Thrombin or factor Xa inhibitors

ABSTRACT

This invention relates generally to inhibitors of trypsin-like serine protease enzymes, especially factor Xa or thrombin, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.

FIELD OF THE INVENTION

This invention relates generally to inhibitors of trypsin-like serine protease enzymes, especially factor Xa or thrombin, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.

BACKGROUND OF THE INVENTION

Activated factor Xa, whose major practical role is the generation of thrombin by the limited proteolysis of prothrombin, holds a central position that links the intrinsic and extrinsic activation mechanisms in the final common pathway of blood coagulation. The generation of thrombin, the final serine protease in the pathway to generate a fibrin clot, from its precursor is amplified by formation of prothrombinase complex (factor Xa, factor V, Ca²⁺ and phospholipid). Since it is calculated that one molecule of factor Xa can generate 138 molecules of thrombin (Elodi, S., Varadi, K.: Optimization of conditions for the catalytic effect of the factor IXa-factor VIII Complex: Probable role of the complex in the amplification of blood coagulation. Thromb. Res. 1979, 15, 617-629), inhibition of factor Xa may be more efficient than inactivation of thrombin in interrupting the blood coagulation system.

Therefore, efficacious and specific inhibitors of factor Xa, thrombin, or both are needed as potentially valuable therapeutic agents for the treatment of thromboembolic disorders. It is thus desirable to discover new factor Xa, thrombin, or both inhibitors.

SUMMARY OF THE INVENTION

Accordingly, one object of the present invention is to provide novel nitrogen containing aromatic heterocycles, with ortho-substituted P1 groups, which are useful as factor Xa inhibitors or pharmaceutically acceptable salts or prodrugs thereof.

It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.

It is another object of the present invention to provide a method for treating thromboembolic disorders comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.

It is another object of the present invention to provide novel compounds for use in therapy.

It is another object of the present invention to provide the use of novel compounds for the manufacture of a medicament for the treatment of thrombosis or a disease mediated by factor Xa.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[1] Thus, in an embodiment, the present invention provides a novel compound selected from the group:

ring D is selected from —(CH₂)₃—, —CH₂CH═CH—, —CH₂N═CH—, and a 5 membered aromatic system containing from 0-2 heteroatoms selected from the group N, O, and S, provided that from 0-1 O and S atoms are present;

ring D is substituted with 0-2 R;

E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, substituted with 0-1 R;

R is selected from Cl, F, Br, I, OH, C₁₋₃ alkoxy, NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂, CH₂CH₂NH₂, CH₂CH₂NH(C₁₋₃ alkyl), and CH₂CH₂N(C₁₋₃ alkyl)₂;

M is selected from the group:

J is O or S;

J^(a) is NH or NR^(1a);

Z is selected from (CR⁸R⁹)₁₋₄, (CR⁸R⁹)_(r)O(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)O(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)OC(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³C(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)OC(O)O(CR⁸R⁹)_(r), (CH₂)_(r)OC(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³C(O)O(CR⁸R⁹)_(r), (CH₂)_(r)NR³C(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)S(O)_(p)(CR⁸R⁹)_(r), (CCR⁸R⁹)_(r)SO₂NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³SO₂(CR⁸R⁹)_(r), and (CR⁸R⁹)_(r)NR³SO₂NR³(CR⁸R⁹)_(r), provided that Z does not form a N—N, N—O, N—S, NCH₂N, NCH₂O, or NCH₂S bond with the groups to which Z is attached;

R^(1a) is selected from H, —(CH₂)_(r)—R¹′, —CH═CH—R¹′, NHCH₂R¹″, OCH₂R¹″, SCH₂R¹″, NH(CH₂)₂(CH₂)_(t)R¹′, O(CH₂)₂(CH₂)_(t)R¹′, and S(CH₂)₂(CH₂)_(t)R¹′;

R¹′ is selected from H, C₁₋₃ alkyl, F, Cl, Br, I, —CN, —CHO, (CF₂)_(r)CF₃, (CH₂)_(r)OR², NR²R^(2a), C(O)R^(2c), OC(O)R², (CF₂)_(r)CO₂R^(2c), S(O)_(p)R^(2b), NR²(CH₂)_(r)OR^(2a), C(═NR^(2c))NR²R^(2a), NR²C(O)R^(2b), NR²C(O)NHR^(2b), NR²C(O)₂R^(2a), OC(O)NR^(2a)R^(2b), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR², SO₂NR²R^(2a), NR²SO₂R^(2b), C₃₋₆ carbocyclic residue substituted with 0-2 R⁴, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R⁴;

R¹″ is selected from H, CH(CH₂OR²)₂, C(O)R^(2c), C(O)NR²R^(2a), S(O)R^(2b), S(O)₂R^(2b), and SO₂NR²R^(2a);

R², at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocyclic residue substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b);

R^(2a), at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl, benzyl, C₃₋₆ cycloalkylmethyl substituted with 0-2 R^(4b), C₃₋₆ carbocyclic residue substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b);

R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxy, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocyclic residue substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b);

R^(2c), at each occurrence, is selected from CF₃, OH, C₁₋₄ alkoxy, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocyclic residue substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b);

alternatively, R² and R^(2a) combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R^(4b) which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;

alternatively, R² and R^(2a), together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R^(4b) and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;

R³, at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl;

R^(3a) at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl;

R^(3b), at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl;

R^(3c), at each occurrence, is selected from C₁₋₄ alkyl, and phenyl;

A is selected from:

C₃₋₁₀ carbocyclic residue substituted with 0-2 R⁴, and

5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R⁴;

B is selected from:

X—Y, NR²R^(2a), C(═NR²)NR²R^(2a), NR²C(═NR²)NR²R^(2a),

C₃₋₁₀ carbocyclic residue substituted with 0-2 R^(4a), and

5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a);

X is selected from C₁₋₄ alkylene, —CR²(CR²R^(2b))(CH₂)_(t)—, —C(O)—, —C(═NR¹″)—, —CR²(NR¹″R²)—, —CR²(OR²)—, —CR²(SR²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —S(O)_(p)—, —S(O)_(p)CR²R^(2a)—, —CR²R^(2a)S(O)_(p)—, —S(O)₂NR²—, —NR²S(O)₂—, —NR²S(O)₂CR²R^(2a)—, —CR²R^(2a)S(O)₂NR²—, —NR²S(O)₂NR²—, —C(O)NR²—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—, —CR²R^(2a)NR²C(O)—, —NR²C(O)O—, —OC(O)NR²—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—;

Y is selected from:

(CH₂)_(r)NR²R^(2a), provided that X—Y do not form a N—N, O—N, or S—N bond,

C₃₋₁₀ carbocyclic residue substituted with 0-2 R^(4a), and

5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a);

R⁴, at each occurrence, is selected from H, ═O, (CH₂)_(r)OR², F, Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), NR²C(O)NR²R^(2a), C(═NR²)NR²R^(2a), C(═NS(O)₂R⁵)NR²R^(2a), NHC(═NR²)NR²R^(2a), C(O)NHC(═NR²)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂—C₁₋₄ alkyl, NR²SO₂R⁵, S(O)_(p)R⁵, (CF₂)_(r)CF₃, NHCH₂R¹″, OCH₂R¹″, SCH₂R¹″, N(CH₂)₂(CH₂)_(t)R¹′, O(CH₂)₂(CH₂)_(t)R¹′, and S(CH₂)₂(CH₂)_(t)R¹′,

alternatively, one R⁴ is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S;

R^(4a), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR², (CH₂)_(r)—F, (CH₂)_(r)—Br, (CH₂)_(r)—Cl, Cl, Br, F, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), C(O)NH(CH₂)₂NR²R^(2a), NR²C(O)NR²R^(2a), C(═NR²)NR²R^(2a), NHC(═NR²)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂—C₁₋₄ alkyl, C(O)NHSO₂—C₁₋₄ alkyl, NR²SO₂R⁵, S(O)_(p)R⁵, and (CF₂)_(r)CF₃;

alternatively, one R^(4a) is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-1 R⁵;

R^(4b), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR³, F, Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³, (CH₂)_(r)C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), NR³C(O)NR³R^(3a), C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂—phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, and (CF₂)_(r)CF₃;

R⁵, at each occurrence, is selected from CF₃, C₁₋₆ alkyl, phenyl substituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶;

R⁶, at each occurrence, is selected from H, OH, (CH₂)_(r)OR², halo, C₁₋₄ alkyl, CN, NO₂, (CH₂)_(r)NR²R^(2a),(CH₂)_(r)C(O)R^(2b), NR²C(O)R^(2b), NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a), NR²SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl;

R⁷, at each occurrence, is selected from H, OH, C₁₋₆ alkyl, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxy, C₁₋₄ alkoxycarbonyl, (CH₂)_(n)-phenyl, C₆₋₁₀ aryloxy, C₆₋₁₀ aryloxycarbonyl, C₆₋₁₀ arylmethylcarbonyl, C₁₋₄ alkylcarbonyloxy C₁₋₄ alkoxycarbonyl, C₆₋₁₀ arylcarbonyloxy C₁₋₄ alkoxycarbonyl, C₁₋₆ alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C₁₋₄ alkoxycarbonyl;

R⁸, at each occurrence, is selected from H, C₁₋₆ alkyl and (CH₂)_(n)-phenyl;

alternatively, R⁷ and R⁸ combine to form a 5 or 6 membered saturated, ring which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;

R⁹, at each occurrence, is selected from H, C₁₋₆ alkyl and (CH₂)_(n)-phenyl;

n, at each occurrence, is selected from 0, 1, 2, and 3;

m, at each occurrence, is selected from 0, 1, and 2;

p, at each occurrence, is selected from 0, 1, and 2;

r, at each occurrence, is selected from 0, 1, 2, and 3;

s, at each occurrence, is selected from 0, 1, and 2; and,

t, at each occurrence, is selected from 0, 1, 2, and 3.

[2] In another embodiment, the present invention provides a novel compound selected from the group:

wherein,

M is selected from the group:

R is selected from H, Cl, F, Br, I, (CH₂)_(t)OR³, C₁₋₄ alkyl, OCF₃, CF₃, C(O)NR⁷R⁸, and (CR⁸R⁹)_(t)NR⁷R⁸;

Z is selected from CH₂O, OCH₂, CH₂NH, NHCH₂, C(O), CH₂C(O), C(O)CH₂, NHC(O), C(O)NH, CH₂S(O)₂, S(O)₂(CH₂), SO₂NH, and NHSO₂, provided that Z does not form a N—N, N—O, NCH₂N, or NCH₂O bond with ring M or group A;

A is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R⁴;

phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, irnidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl;

B is selected from: H, Y, and X—Y;

X is selected from C₁₋₄ alkylene, —C(O)—, —C(═NR)—, —CR²(NR²R^(2a))—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —C(O)NR²—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—, —CR²R^(2a)NR²C(O)—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—;

Y is NR²R^(2a) or CH₂NR²R^(2a), provided that X—Y do not form a N—N or O—N bond;

alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R^(4a);

cylcopropyl, cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl;

alternatively, Y is selected from the following bicyclic heteroaryl ring systems:

K is selected from O, S, NH, and N.

[3] In another embodiment, the present invention provides a novel compound selected from the group:

M is selected from the group:

Z is C(O)CH₂ and CONH, provided that Z does not form a N—N bond with group A;

A is selected from phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2 R⁴; and,

B is selected from Y, X—Y, phenyl, pyrrolidino, morpholino, 1,2,3-triazolyl, and imidazolyl, and is substituted with 0-1 R^(4a);

B is selected from: Y and X—Y;

X is selected from CH₂, —C(O), and O;

Y is NR²R^(2a) or CH₂NR²R^(2a), provided that X—Y does not form an O—N bond;

alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R^(4a);

phenyl, piperazinyl, pyridyl, pyrimidyl, morpholinyl, pyrrolidinyl, imidazolyl, and 1,2,3-triazolyl;

R², at each occurrence, is selected from H, CF₃, CH₃, benzyl, and phenyl;

R^(2a), at each occurrence, is selected from H, CF₃, CH₃, CH(CH₃)₂, cyclopropylmethyl, benzyl, and phenyl;

alternatively, R² and R^(2a) combine to form a ring system substituted with 0-2 R^(4b), the ring system being selected from pyrrolidinyl, piperazinyl and morpholino;

R⁴, at each occurrence, is selected from OH, (CH₂)_(r)OR², Cl, F, C₁₋₄ alkyl, (CH₂)_(r)NR²R^(2a), and (CF₂)_(r)CF₃;

R^(4a) is selected from Cl, F, C₁₋₄ alkyl, CF₃, (CH₂)_(r)NR²R^(2a), S(O)_(p)R⁵, SO₂NR²R^(2a), and 1-CF₃-tetrazol-2-yl;

R^(4b), at each occurrence, is selected from OH, Cl, F, CH₃, and CF₃;

R⁵, at each occurrence, is selected from CF₃, C₁₋₆ alkyl, phenyl, and benzyl;

R⁷, at each occurrence, is selected from H, CH₃, and CH₂CH₃; and,

R⁸, at each occurrence, is selected from H and CH₃.

[4] In another embodiment, the present invention provides a novel compound wherein:

M is selected from the group:

J is N;

R^(1a) is absent or is —(CH₂)_(r)-R¹′;

R¹′ is selected from H, C₁₋₃ alkyl, F, Cl, —CN, CF₃, (CH₂)_(r)OR², NR²R^(2a), C(O)R^(2c), OC(O)R², S(O)_(p)R^(2b), NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a), C₃₋₆ carbocyclic residue substituted with 0-2 R^(4a), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a);

A is selected from the group: phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl; and,

B is selected from the group: 2-CF₃-phenyl, 2-(aminosulfonyl)phenyl, 2-(methylaminosulfonyl)phenyl, 2-(dimethylaminosulfonyl)phenyl, 1-pyrrolidinocarbonyl, 2-(methylsulfonyl)phenyl, 2-(N,N-dimethylaminomethyl)phenyl, 2-(isopropylaminomethyl)phenyl, 2-(cyclopropylaminomethyl)phenyl, 2-(N-pyrrolidinylmethyl)phenyl, 2-(3-hydroxy-N-pyrrolidinylmethyl)phenyl, 4-morpholino, 2-(1′-CF₃-tetrazol-2-yl)phenyl, 4-morpholinocarbonyl, 1-methyl-2-imidazolyl, 2-methyl-1-imidazolyl, 5-methyl-1-imidazolyl, 2-(N,N-dimethylaminomethyl)imidazolyl, 2-methylsulfonyl-1-imidazolyl and, 5-methyl-1,2,3-triazolyl.

In another embodiment, the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of present invention or a pharmaceutically acceptable salt form thereof.

In another embodiment, the present invention provides a novel method for treating or preventing a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt form thereof.

Definitions

The compounds herein described may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins, C═N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated. All processes used to prepare compounds of the present invention and intermediates made therein are considered to be part of the present invention.

“Substituted” is intended to indicate that one or more hydrogens on the atom indicated in the expression using “substituted” is replaced with a selection from the indicated group(s), provided that the indicated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., ═O) group, then 2 hydrogens on the atom are replaced.

The present invention is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium. Isotopes of carbon include C-13 and C-14.

When any variable (e.g., R⁶) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R⁶, then said group may optionally be substituted with up to two R⁶ groups and R⁶ at each occurrence is selected independently from the definition of R⁶. Also, combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.

When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom on the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such substituent. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.

As used herein, “alkyl” or “alkylene” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. C₁₋₁₀ alkyl (or alkylene), is intended to include C₁, C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, and C₁₀ alkyl groups. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl. “Haloalkyl” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more halogen (for example —C_(v)F_(w) where v=1 to 3 and w=1 to (2v+1)). Examples of haloalkyl include, but are not limited to, trifluoromethyl, trichloromethyl, pentafluoroethyl, and pentachloroethyl. “Alkoxy” represents an alkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge. C₁₋₁₀ alkoxy, is intended to include C₁, C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, and C₁₀ alkoxy groups. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy. “Cycloalkyl” is intended to include saturated ring groups, such as cyclopropyl, cyclobutyl, or cyclopentyl. C₃₋₇ cycloalkyl, is intended to include C₃, C₄, C₅, C₆, and C₇ cycloalkyl groups. “Alkenyl” or “alkenylene” is intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain, such as ethenyl and propenyl. C₂₋₁₀ alkenyl (or alkenylene), is intended to include C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, and C₁₀ alkenyl groups. “Alkynyl” or “alkynylene” is intended to include hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain, such as ethynyl and propynyl. C₂₋₁₀ alkynyl (or alkynylene), is intended to include C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, and C₁₀ alkynyl groups.

“Halo” or “halogen” as used herein refers to fluoro, chloro, bromo, and iodo; and “counterion” is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, and sulfate.

As used herein, “carbocycle” or “carbocyclic group” is intended to mean any stable 3, 4, 5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, 10, 11, 12, or 13-membered bicyclic or tricyclic, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, and tetrahydronaphthyl.

As used herein, the term “heterocycle” or “heterocyclic group” is intended to mean a stable 5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, or 10-membered bicyclic heterocyclic ring which is saturated, partially unsaturated or unsaturated (aromatic), and which consists of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, NH, O and S and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. A nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1. As used herein, the term “aromatic heterocyclic group” or “heteroaryl” is intended to mean a stable 5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, or 10-membered bicyclic heterocyclic aromatic ring which consists of carbon atoms and 1, 2, 3, or 4 heterotarns independently selected from the group consisting of N, NH, O and S. It is to be noted that total number of S and O atoms in the aromatic heterocycle is not more than 1.

Examples of heterocycles include, but are not limited to, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles.

The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.

The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the disclosure of which is hereby incorporated by reference.

“Prodrugs” are intended to include any covalently bonded carriers which release the active parent drug according to formula (I) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of a compound of formula (I) are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of formula (I) wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug or compound of formula (I) is administered to a mammalian subject, cleaves to form a free hydroxyl, free amino, or free sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of formula (I), and the like.

“Stable compound” and “stable structure” are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

“Therapeutically effective amount” is intended to include an amount of a compound of the present invention or an amount of the combination of compounds claimed effective to inhibit factor Xa or thrombin or treat diseases related to factor Xa or thrombin in a host. The combination of compounds is preferably a synergistic combination. Synergy, as described for example by Chou and Talalay, Adv. Enzyme Regul. 22:27-55 (1984), occurs when the effect (in this case, inhibition of factor Xa or thrombin) of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at suboptimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased antiviral effect, or some other beneficial effect of the combination compared with the individual components.

Synthesis

The compounds of the present invention can be prepared in a number of ways known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or by variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those described below. The reactions are performed in a solvent appropriate to the reagents and materials employed and suitable for the transformations being effected. It will be understood by those skilled in the art of organic synthesis that the functionality present on the molecule should be consistent with the transformations proposed. This will sometimes require a judgment to modify the order of the synthetic steps or to select one particular process scheme over another in order to obtain a desired compound of the invention. It will also be recognized that another major consideration in the planning of any synthetic route in this field is the judicious choice of the protecting group used for protection of the reactive functional groups present in the compounds described in this invention. An authoritative account describing the many alternatives to the trained practitioner is Greene and Wuts (Protective Groups In Organic Synthesis, Wiley and Sons, 1991). All references cited herein are hereby incorporated in their entirety herein by reference.

Compounds wherein rings D—E are A or B, shown below:

can be prepared via the methodology outlined in Scheme I below.

Removal of the amino protecting group followed by further manipulation can afford key starting materials wherein the amino is a benzylamine or alpha-amino acid or all analogs stated earlier. The starting material can also be obtained from intermediate 4 via an SN2 type displacement of the o-tosylate. Decarboxylation of intermediate 3 affords the ketone analog that also can be further manipulated to afford additional starting materials D—E. Coupling of analogs such as intermediate 7 via standard techniques followed by displacement of the phenoxy pyridine via standard techniques known to those in the art should afford the compounds of formula A. Chiral compounds can be separated via chiral HPLC techniques or by co-crystallization methods with a known chiral precursor.

Compounds wherein D—E is of formula B as shown above can be prepared as shown in Scheme II.

Via this scheme amino intermediates such as 3(B) and phenoxy analogs 6 and 7 can be obtained easily via the methods previously described. These intermediates can be further coupled to requisite precursors followed by conversion of the phenoxy group to an amino via standard techniques to afford the amino-pyridyl compounds of formula 1-3.

The unsaturated analogs can be prepared according to Scheme III.

Intermediate 3 can be further manipulated to afford other D—E intermediates via methods described previously. In a similar fashion the other unsaturated analog can be prepared via Scheme IV shown below.

Scheme V describes the preparation of 3-aminobenzofuran intermediates.

4-benzyloxy-2(1H)-pyridone (available from Aldrich) can be converted to the aminopyridine derivative using standard procedures known to the practitioners of the art. Debenzylation, coupling with bromoethylacetate, followed by basic hydrolysis affords an intermediate that undergoes the Friedel-Crafts acylation.

Scheme VI describes the preparation of indole intermediates.

Scheme VII describes the preparation of 3-halo-4-aminobenzothiophene intermediates.

Scheme VIII describes the preparation of 1-substituted-7-amino-azabenzimidazole intermediates.

Scheme X describes the preparation of 2-substituted-7-amino-azabenzimidazole intermediates.

Scheme XI describes the preparation of 5-aminobenzisoxazole intermediates.

Synthesis of 5-aminobenzisoxazoles in which the 3-position may be a protected amine could be accomplished starting from the commercially available 3-cyano4-fluoronitrobenzene. Displacement of flourine with acetohydroxamic acid under basic conditions followed by ring closure by subsequent addition to the nitrile would yield the benzisoxazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XII describes the preparation of 5-aminoindazole intermediates.

Synthesis of 5-aminoindazoles in which the 3-position may be a protected amine could be accomplished starting from the commercially available 3-cyano4-fluoronitrobenzene. Displacement of flourine with hydrazine followed by ring closure by subsequent addition to the nitrile would yield the indazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XIII describes the preparation of 5-aminobenzisothiazole intermediates.

Synthesis of 5-aminobenzisothiazoles in which the 3-position may be a protected amine could be accomplished starting from the commercially available 2-benzylthio-5-nitrobenzonitrile. Conversion of the aryl nitrile to benzamidine, sulfoxide formation and ring closure/debenzylation would yield the benzisothiazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XIV describes the preparation of 6-aminobenzisoxazoleintermediates.

Synthesis of 6-aminobenzisoxazoles in which the 3-position may be a protected amine could be accomplished starting from commercially available 2-fluoro-4-nitrobenzoic acid. Conversion of carboxylic acid to nitrile via standard manipulations would give 2-fluoro-4-nitrobenzonitrile. Displacement of flourine with acetohydroxamic acid under basic conditions followed by ring closure by subsequent addition to the nitrile would yield the benzisoxazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XV describes the preparation of 5-aminoindazole intermediates.

Synthesis of 5-aminoindazoles in which the 3-position may be a protected amine could be accomplished starting from from 2-fluoro-4-nitrobenzonitrile whose synthesis is described elsewhere in this patent. Displacement of flourine with hydrazine followed by ring closure by subsequent addition to the nitrile would yield the indazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XVI describes the preparation of 6-aminobenzisothiazole intermediates.

Synthesis of 6-aminobenzisothiazoles in which the 3-position may be a protected amine could be accomplished starting from 2-fluoro-4-nitrobenzonitrile whose synthesis is described elsewhere in this patent. Displacement of flourine with benzylthio anion yields 2-benzylthio-4-nitrobenzonitrile. Conversion of the aryl nitrile to benzamidine, sulfoxide formation and ring closure/debenzylation would yield the benzisothiazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XVII describes the preparation of 6-aminoisoindole intermediates.

Synthesis of 6-aminoisoindoles in which the 1-position may be a protected amine could be accomplished starting from commercially available 2-cyano4-nitrotoluene. Bromination of tolyl methyl to give a benzyl bromide followed by displacement with azide and reduction to benzylamine would cyclize to the isoindole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XVIII describes the preparation of 5-aminoisoindole intermediates.

Synthesis of 5-aminoisoindoles in which the 1-position may be a protected amine could be accomplished starting from commercially available 2-cyano-5-nitrotoluene. Bromination of tolyl methyl to give a benzyl bromide followed by displacement with azide and reduction to benzylamine would cyclize to the isoindole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XIX describes the preparation of 2-aminoindole derivatives a intermediates.

Synthesis of the desired compounds in which the 4-position may be a protected amine could be accomplished starting from the commercially available furan or thiophene. Using literature methods (J. Med. Chem. 1989, 32, 1147) one could obtain the 2-nitro-4-chloro-furo or thieno<3,2-c>pyridine. Displacement of the 4-chloro with phenoxide then conversion to 4-amino followed by suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XX describes the preparation of 2-amino-1-H-pyrrolo[3,2-c]pyridine intermediates.

Synthesis of 2-amino-1-H-pyrrolo[3,2-c]pyridine in which the 4-position may be a protected amine could be accomplished starting from the commercially available pyrrole-2-carboxaldehyde. Nitration and protection of pyrrole nitrogen with P1 would afford the nitro/aldehyde intermediate. Using literature methods (J. Med. Chem. 1989, 32, 1147) one could obtain the 2-nitro-4-chloro-pyrrolo[3,2-c]pyridine. Displacement of the 4-chloro with phenoxide then conversion to 4-amino followed by suitable protection and reduction of the aryl nitro group would provide the desired compound.

BOC-Protected aminobenzisoxazolemethylbromide can be reacted with the lithium salt of acetonitrile to give the nitrile. The nitrile can be further reacted in a similar fashion as in WO96/16940 to give the desired compound.

The compounds of the present invention have a group “A—B” attached to ring M. Preparations of some of the rings M and the “A—B” moieties can follow the same methods described in WO97/23212, WO97/30971, WO97/38984, WO98/01428, WO98/06694, WO98/28269, WO98/28282, WO98/57934, WO98/57937, and WO98/57951, the contents of which are incorporated herein by reference. Preparations of the some of the rings M can also follow the same methods described in WO98/28269, WO98/57951, and WO98/57937, the contents of which are incorporated herein by reference. Compounds of Formula I can be prepared by reacting an appropriate 6-5 system described above with an appropriate intermediate to either form the desired ring M or to be attached to desired ring M. The above noted publications describe conditions for coupling ring M and a desired 6-5 system.

Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments which are given for illustration of the invention and are not intended to be limiting thereof.

Utility

The compounds of this invention are useful as anticoagulants for the treatment or prevention of thromboembolic disorders in mammals. The term “thromboembolic disorders” as used herein includes arterial or venous cardiovascular or cerebrovascular thromboembolic disorders, including, for example, unstable angina, first or recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary and cerebral arterial thrombosis, cerebral embolism, kidney embolisms, and pulmonary embolisms. The anticoagulant effect of compounds of the present invention is believed to be due to inhibition of factor Xa, thrombin, or both.

The effectiveness of compounds of the present invention as inhibitors of factor Xa can be determined using purified human factor Xa and synthetic substrate. The rate of factor Xa hydrolysis of chromogenic substrate S2222 (Kabi Pharmacia, Franklin, Ohio) can be measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA, which can be monitored spectrophotometrically by measuring the increase in absorbance at 405 nM. A decrease in the rate of absorbance change at 405 nm in the presence of inhibitor is indicative of enzyme inhibition. The results of this assay are expressed as inhibitory constant, K_(i).

Factor Xa determinations were made in 0.10 M sodium phosphate buffer, pH 7.5, containing 0.20 M NaCl, and 0.5% PEG 8000. The Michaelis constant, K_(m), for substrate hydrolysis can be determined at 25° C. using the method of Lineweaver and Burk. Values of K_(i) were determined by allowing 0.2-0.5 nM human factor Xa (Enzyme Research Laboratories, South Bend, Ind.) to react with the substrate (0.20 mM-1 mM) in the presence of inhibitor. Reactions were allowed to go for 30 minutes and the velocities (rate of absorbance change vs time) were measured in the time frame of 25-30 minutes. The following relationship can be used to calculate K_(i) values:

(v _(o) −v _(s))/v _(s) =I(K _(i)(1+S/K _(m)))

where:

v_(o) is the velocity of the control in the absence of inhibitor;

v_(s) is the velocity in the presence of inhibitor;

I is the concentration of inhibitor;

K_(i) is the dissociation constant of the enzyme:inhibitor complex;

S is the concentration of substrate;

K_(m) is the Michaelis constant.

Compounds tested in the above assay are considered to be active if they exhibit a K_(i) of ≦10 μM. Preferred compounds of the present invention have K_(i)'s of ≦1 μM. More preferred compounds of the present invention have K_(i)'s of ≦0.1 μM. Even more preferred compounds of the present invention have K_(i)'s of ≦0.01 μM. Still more preferred compounds of the present invention have K_(i)'s of ≦0.001 μM.

The antithrombotic effect of compounds of the present invention can be demonstrated in a rabbit arterio-venous (AV) shunt thrombosis model. In this model, rabbits weighing 2-3 kg anesthetized with a mixture of xylazine (10 mg/kg i.m.) and ketamine (50 mg/kg i.m.) are used. A saline-filled AV shunt device is connected between the femoral arterial and the femoral venous cannulae. The AV shunt device consists of a piece of 6-cm tygon tubing which contains a piece of silk thread. Blood will flow from the femoral artery via the AV-shunt into the femoral vein. The exposure of flowing blood to a silk thread will induce the formation of a significant thrombus. After forty minutes, the shunt is disconnected and the silk thread covered with thrombus is weighed. Test agents or vehicle will be given (i.v., i.p., s.c., or orally) prior to the opening of the AV shunt. The percentage inhibition of thrombus formation is determined for each treatment group. The ID50 values (dose which produces 50% inhibition of thrombus formation) are estimated by linear regression.

The compounds of formula (I) may also be useful as inhibitors of serine proteases, notably human thrombin, plasma kallikrein and plasmin. Because of their inhibitory action, these compounds are indicated for use in the prevention or treatment of physiological reactions, blood coagulation and inflammation, catalyzed by the aforesaid class of enzymes. Specifically, the compounds have utility as drugs for the treatment of diseases arising from elevated thrombin activity such as myocardial infarction, and as reagents used as anticoagulants in the processing of blood to plasma for diagnostic and other commercial purposes.

Compounds of the present invention can be shown to be direct acting inhibitors of the serine protease thrombin by their ability to inhibit the cleavage of small molecule substrates by thrombin in a purified system. In vitro inhibition constants were determined by the method described by Kettner et al. in J. Biol. Chem. 265, 18289-18297 (1990), herein incorporated by reference. In these assays, thrombin-mediated hydrolysis of the chromogenic substrate S2238 (Helena Laboratories, Beaumont, Tex.) can be monitored spectrophotometrically. Addition of an inhibitor to the assay mixture results in decreased absorbance and is indicative of thrombin inhibition. Human thrombin (Enzyme Research Laboratories, Inc., South Bend, Ind.) at a concentration of 0.2 nM in 0.10 M sodium phosphate buffer, pH 7.5, 0.20 M NaCl, and 0.5% PEG 6000, can be incubated with various substrate concentrations ranging from 0.20 to 0.02 mM. After 25 to 30 minutes of incubation, thrombin activity can be assayed by monitoring the rate of increase in absorbance at 405 nm which arises owing to substrate hydrolysis. Inhibition constants were derived from reciprocal plots of the reaction velocity as a function of substrate concentration using the standard method of Lineweaver and Burk.

Compounds tested in the above assay are considered to be active if they exhibit a K_(i) of ≦10 μM. Preferred compounds of the present invention have K_(i)'s of ≦1 μM. More preferred compounds of the present invention have K_(i)'s of ≦0.1 μM. Even more preferred compounds of the present invention have K_(i)'s of ≦0.01 μM. Still more preferred compounds of the present invention have K_(i)'s of ≦0.001 μM.

The compounds of the present invention can be administered alone or in combination with one or more additional therapeutic agents. These include other anticoagulant or coagulation inhibitory agents, anti-platelet or platelet inhibitory agents, thrombin inhibitors, or thrombolytic or fibrinolytic agents.

The compounds are administered to a mammal in a therapeutically effective amount. By “therapeutically effective amount” it is meant an amount of a compound of Formula I that, when administered alone or in combination with an additional therapeutic agent to a mammal, is effective to prevent or ameliorate the thromboembolic disease condition or the progression of the disease.

By “administered in combination” or “combination therapy” it is meant that the compound of Formula I and one or more additional therapeutic agents are administered concurrently to the mammal being treated. When administered in combination each component may be administered at the same time or sequentially in any order at different points in time. Thus, each component may be administered separately but sufficiently closely in time so as to provide the desired therapeutic effect. Other anticoagulant agents (or coagulation inhibitory agents) that may be used in combination with the compounds of this invention include warfarin and heparin, as well as other factor Xa inhibitors such as those described in the publications identified above under Background of the Invention.

The term anti-platelet agents (or platelet inhibitory agents), as used herein, denotes agents that inhibit platelet function such as by inhibiting the aggregation, adhesion or granular secretion of platelets. Such agents include, but are not limited to, the various known non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, sulindac, indomethacin, mefenamate, droxicam, diclofenac, sulfinpyrazone, and piroxicam, including pharmaceutically acceptable salts or prodrugs thereof. Of the NSAIDS, aspirin (acetylsalicyclic acid or ASA), and piroxicam are preferred. Other suitable anti-platelet agents include ticlopidine, including pharmaceutically acceptable salts or prodrugs thereof Ticlopidine is also a preferred compound since it is known to be gentle on the gastro-intestinal tract in use. Still other suitable platelet inhibitory agents include IIb/IIIa antagonists, thromboxane-A2-receptor antagonists and thromboxane-A2-synthetase inhibitors, as well as pharmaceutically acceptable salts or prodrugs thereof.

The term thrombin inhibitors (or anti-thrombin agents), as used herein, denotes inhibitors of the serine protease thrombin. By inhibiting thrombin, various thrombin-mediated processes, such as thrombin-mediated platelet activation (that is, for example, the aggregation of platelets, and/or the granular secretion of plasminogen activator inhibitor-1 and/or serotonin) and/or fibrin formation are disrupted. A number of thrombin inhibitors are known to one of skill in the art and these inhibitors are contemplated to be used in combination with the present compounds. Such inhibitors include, but are not limited to, boroarginine derivatives, boropeptides, heparins, hirudin and argatroban, including pharmaceutically acceptable salts and prodrugs thereof. Boroarginine derivatives and boropeptides include N-acetyl and peptide derivatives of boronic acid, such as C-terminal a-aminoboronic acid derivatives of lysine, ornithine, arginine, homoarginine and corresponding isothiouronium analogs thereof. The term hirudin, as used herein, includes suitable derivatives or analogs of hirudin, referred to herein as hirulogs, such as disulfatohirudin. Boropeptide thrombin inhibitors include compounds described in Kettner et al., U.S. Pat. No. 5,187,157 and EP 293 881 A2, the disclosures of which are hereby incorporated herein by reference. Other suitable boroarginine derivatives and boropeptide thrombin inhibitors include those disclosed in WO92/07869 and EP 471,651 A2, the disclosures of which are hereby incorporated herein by reference.

The term thrombolytics (or fibrinolytic) agents (or thrombolytics or fibrinolytics), as used herein, denotes agents that lyse blood clots (thrombi). Such agents include tissue plasminogen activator, anistreplase, urokinase or streptokinase, including pharmaceutically acceptable salts or prodrugs thereof. The term anistreplase, as used herein, refers to anisoylated plasminogen streptokinase activator complex, as described, for example, in European Patent Application No. 028,489, the disclosure of which is hereby incorporated herein by reference herein. The term urokinase, as used herein, is intended to denote both dual and single chain urokinase, the latter also being referred to herein as prourokinase.

Administration of the compounds of Formula I of the invention in combination with such additional therapeutic agent, may afford an efficacy advantage over the compounds and agents alone, and may do so while permitting the use of lower doses of each. A lower dosage minimizes the potential of side effects, thereby providing an increased margin of safety.

The compounds of the present invention are also useful as standard or reference compounds, for example as a quality standard or control, in tests or assays involving the inhibition of factor Xa. Such compounds may be provided in a commercial kit, for example, for use in pharmaceutical research involving factor Xa. For example, a compound of the present invention could be used as a reference in an assay to compare its known activity to a compound with an unknown activity. This would ensure the experimenter that the assay was being performed properly and provide a basis for comparison, especially if the test compound was a derivative of the reference compound. When developing new assays or protocols, compounds according to the present invention could be used to test their effectiveness.

The compounds of the present invention may also be used in diagnostic assays involving factor Xa. For example, the presence of factor Xa in an unknown sample could be determined by addition of chromogenic substrate S2222 to a series of solutions containing test sample and optionally one of the compounds of the present invention. If production of pNA is observed in the solutions containing test sample, but not in the presence of a compound of the present invention, then one would conclude factor Xa was present.

Dosage and Formulation

The compounds of this invention can be administered in such oral dosage forms as tablets, capsules (each of which includes sustained release or timed release formulations), pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions. They may also be administered in intravenous (bolus or infusion), intraperitoneal, subcutaneous, or intramuscular form, all using dosage forms well known to those of ordinary skill in the pharmaceutical arts. They can be administered alone, but generally will be administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice.

The dosage regimen for the compounds of the present invention will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the species, age, sex, health, medical condition, and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; the route of administration, the renal and hepatic function of the patient,and the effect desired. A physician or veterinarian can determine and prescribe the effective amount of the drug required to prevent, counter, or arrest the progress of the thromboembolic disorder.

By way of general guidance, the daily oral dosage of each active ingredient, when used for the indicated effects, will range between about 0.001 to 1000 mg/kg of body weight, preferably between about 0.01 to 100 mg/kg of body weight per day, and most preferably between about 1.0 to 20 mg/kg/day. Intravenously, the most preferred doses will range from about 1 to about 10 mg/kg/minute during a constant rate infusion. Compounds of this invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three, or four times daily.

Compounds of this invention can be administered in intranasal form via topical use of suitable intranasal vehicles, or via transdermal routes, using transdermal skin patches. When administered in the form of a transdernal delivery system, the dosage administration will, of course, be continuous rather than intermittent throughout the dosage regimen.

The compounds are typically administered in admixture with suitable pharmaceutical diluents, excipients, or carriers (collectively referred to herein as pharmaceutical carriers) suitably selected with respect to the intended form of administration, that is, oral tablets, capsules, elixirs, syrups and the like, and consistent with conventional pharmaceutical practices.

For instance, for oral administration in the form of a tablet or capsule, the active drug component can be combined with an oral, non-toxic, pharmaceutically acceptable, inert carrier such as lactose, starch, sucrose, glucose, methyl callulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like; for oral administration in liquid form, the oral drug components can be combined with any oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Moreover, when desired or necessary, suitable binders, lubricants, disintegrating agents, and coloring agents can also be incorporated into the mixture. Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth, or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

The compounds of the present invention can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines.

Compounds of the present invention may also be coupled with soluble polymers as targetable drug carriers. Such polymers can include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylaspartamidephenol, or polyethyleneoxide-polylysine substituted with palmitoyl residues. Furthermore, the compounds of the present invention may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, and crosslinked or amphipathic block copolymers of hydrogels.

Dosage forms (pharmaceutical compositions) suitable for administration may contain from about 1 milligram to about 100 milligrams of active ingredient per dosage unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition.

Gelatin capsules may contain the active ingredient and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract.

Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance.

In general, water, a suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, buffer substances. Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium EDTA. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.

Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, a standard reference text in this field.

Representative useful pharmaceutical dosage-forms for administration of the compounds of this invention can be illustrated as follows:

Capsules

A large number of unit capsules can be prepared by filling standard two-piece hard gelatin capsules each with 100 milligrams of powdered active ingredient, 150 milligrams of lactose, 50 milligrams of cellulose, and 6 milligrams magnesium stearate.

Soft Gelatin Capsules

A mixture of active ingredient in a digestable oil such as soybean oil, cottonseed oil or olive oil may be prepared and injected by means of a positive displacement pump into gelatin to form soft gelatin capsules containing 100 milligrams of the active ingredient. The capsules should be washed and dried.

Tablets

Tablets may be prepared by conventional procedures so that the dosage unit is 100 milligrams of active ingredient, 0.2 milligrams of colloidal silicon dioxide, 5 milligrams of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch and 98.8 milligrams of lactose. Appropriate coatings may be applied to increase palatability or delay absorption.

Injectable

A parenteral composition suitable for administration by injection may be prepared by stirring 1.5% by weight of active ingredient in 10% by volume propylene glycol and water. The solution should be made isotonic with sodium chloride and sterilized.

Suspension

An aqueous suspension can be prepared for oral administration so that each 5 mL contain 100 mg of finely divided active ingredient, 200 mg of sodium carboxymethyl cellulose, 5 mg of sodium benzoate, 1.0 g of sorbitol solution, U.S.P., and 0.025 mL of vanillin.

Where the compounds of this invention are combined with other anticoagulant agents, for example, a daily dosage may be about 0.1 to 100 milligrams of the compound of Formula I and about 1 to 7.5 milligrams of the second anticoagulant, per kilogram of patient body weight. For a tablet dosage form, the compounds of this invention generally may be present in an amount of about 5 to 10 milligrams per dosage unit, and the second anti-coagulant in an amount of about 1 to 5 milligrams per dosage unit.

Where the compounds of Formula I are administered in combination with an anti-platelet agent, by way of general guidance, typically a daily dosage may be about 0.01 to 25 milligrams of the compound of Formula I and about 50 to 150 milligrams of the anti-platelet agent, preferably about 0.1 to 1 milligrams of the compound of Formula I and about to 3 milligrams of antiplatelet agents, per kilogram of patient body weight.

Where the compounds of Formula I are adminstered in combination with thrombolytic agent, typically a daily dosage may be about 0.1 to 1 milligrams of the compound of Formula I, per kilogram of patient body weight and, in the case of the thrombolytic agents, the usual dosage of the thrombolyic agent when administered alone may be reduced by about 70-80% when administered with a compound of Formula I.

Where two or more of the foregoing second therapeutic agents are administered with the compound of Formula I, generally the amount of each component in a typical daily dosage and typical dosage form may be reduced relative to the usual dosage of the agent when administered alone, in view of the additive or synergistic effect of the therapeutic agents when administered in combination.

Particularly when provided as a single dosage unit, the potential exists for a chemical interaction between the combined active ingredients. For this reason, when the compound of Formula I and a second therapeutic agent are combined in a single dosage unit they are formulated such that although the active ingredients are combined in a single dosage unit, the physical contact between the active ingredients is minimized (that is, reduced). For example, one active ingredient may be enteric coated. By enteric coating one of the active ingredients, it is possible not only to minimize the contact between the combined active ingredients, but also, it is possible to control the release of one of these components in the gastrointestinal tract such that one of these components is not released in the stomach but rather is released in the intestines. One of the active ingredients may also be coated with a material which effects a sustained-release throughout the gastrointestinal tract and also serves to minimize physical contact between the combined active ingredients. Furthermore, the sustained-released component can be additionally enteric coated such that the release of this component occurs only in the intestine. Still another approach would involve the formulation of a combination product in which the one component is coated with a sustained and/or enteric release polymer, and the other component is also coated with a polymer such as a low viscosity grade of hydroxypropyl methylcellulose (HPMC) or other appropriate materials as known in the art, in order to further separate the active components. The polymer coating serves to form an additional barrier to interaction with the other component.

These as well as other ways of minimizing contact between the components of combination products of the present invention, whether administered in a single dosage form or administered in separate forms but at the same time by the same manner, will be readily apparent to those skilled in the art, once armed with the present disclosure.

The following tables contain representative examples of the present invention. Each entry in each table is intended to be paired with each formulae at the start of the table. For example, example 1 of Table 1 is intended to be paired with each of the formulae shown in Table 1. Example 1 of Table 2 is intended to be paired with each of the formulae shown in Table 2.

The following nomenclature is intended for group A in the following tables.

TABLE 1

Ex # R^(1a) A B   1 CH3 phenyl 2-(aminosulfonyl)phenyl   2 CH3 phenyl 2-(methylaminosulfonyl)phenyl   3 CH3 phenyl 1-pyrrolidinocarbonyl   4 CH3 phenyl 2-(methylsulfonyl)phenyl   5 CH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl   6 CH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl   7 CH3 phenyl 1-methyl-2-imidazolyl   8 CH3 phenyl 2-methyl-1-imidazolyl   9 CH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl  10 CH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  11 CH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  12 CH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  13 CH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  14 CH3 2-pyridyl 2-(aminosulfonyl)phenyl  15 CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl  16 CH3 2-pyridyl 1-pyrrolidinocarbonyl  17 CH3 2-pyridyl 2-(methylsulfonyl)phenyl  18 CH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  19 CH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  20 CH3 2-pyridyl 1-methyl-2-imidazolyl  21 CH3 2-pyridyl 2-methyl-1-imidazolyl  22 CH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  23 CH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  24 CH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  25 CH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  26 CH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  27 CH3 3-pyridyl 2-(aminosulfonyl)phenyl  28 CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl  29 CH3 3-pyridyl 1-pyrrolidinocarbonyl  30 CH3 3-pyridyl 2-(methylsulfonyl)phenyl  31 CH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  32 CH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  33 CH3 3-pyridyl 1-methyl-2-imidazolyl  34 CH3 3-pyridyl 2-methyl-1-imidazolyl  35 CH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  36 CH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  37 CH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  38 CH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  39 CH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  40 CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl  41 CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  42 CH3 2-pyrimidyl 1-pyrrolidinocarbonyl  43 CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl  44 CH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  45 CH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  46 CH3 2-pyrimidyl 1-methyl-2-imidazolyl  47 CH3 2-pyrimidyl 2-methyl-1-imidazolyl  48 CH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  49 CH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  50 CH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  51 CH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  52 CH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  53 CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl  54 CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  55 CH3 5-pyrimidyl 1-pyrrolidinocarbonyl  56 CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl  57 CH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  58 CH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  59 CH3 5-pyrimidyl 1-methyl-2-imidazolyl  60 CH3 5-pyrimidyl 2-methyl-1-imidazolyl  61 CH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  62 CH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  63 CH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  64 CH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  65 CH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  66 CH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl  67 CH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl  68 CH3 2-Cl-phenyl 1-pyrrolidinocarbonyl  69 CH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl  70 CH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl  71 CH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl  72 CH3 2-Cl-phenyl 1-methyl-2-imidazolyl  73 CH3 2-Cl-phenyl 2-methyl-1-imidazolyl  74 CH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  75 CH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  76 CH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  77 CH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  78 CH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  79 CH3 2-F-phenyl 2-(aminosulfonyl)phenyl  80 CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl  81 CH3 2-F-phenyl 1-pyrrolidinocarbonyl  82 CH3 2-F-phenyl 2-(methylsulfonyl)phenyl  83 CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  84 CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  85 CH3 2-F-phenyl 1-methyl-2-imidazolyl  86 CH3 2-F-phenyl 2-methyl-1-imidazolyl  87 CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  88 CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  89 CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  90 CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  91 CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  92 CH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  93 CH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  94 CH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl  95 CH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  96 CH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  97 CH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  98 CH3 2,6-diF-phenyl 1-methyl-2-imidazolyl  99 CH3 2,6-diF-phenyl 2-methyl-1-imidazolyl  100 CH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  101 CH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  102 CH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  103 CH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  104 CH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  105 CH2CH3 phenyl 2-(aminosulfonyl)phenyl  106 CH2CH3 phenyl 2-(methylaminosulfonyl)phenyl  107 CH2CH3 phenyl 1-pyrrolidinocarbonyl  108 CH2CH3 phenyl 2-(methylsulfonyl)phenyl  109 CH2CH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl  110 CH2CH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl  111 CH2CH3 phenyl 1-methyl-2-imidazolyl  112 CH2CH3 phenyl 2-methyl-1-imidazolyl  113 CH2CH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl  114 CH2CH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  115 CH2CH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  116 CH2CH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  117 CH2CH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  118 CH2CH3 2-pyridyl 2-(aminosulfonyl)phenyl  119 CH2CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl  120 CH2CH3 2-pyridyl 1-pyrrolidinocarbonyl  121 CH2CH3 2-pyridyl 2-(methylsulfonyl)phenyl  122 CH2CH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  123 CH2CH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  124 CH2CH3 2-pyridyl 1-methyl-2-imidazolyl  125 CH2CH3 2-pyridyl 2-methyl-1-imidazolyl  126 CH2CH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  127 CH2CH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  128 CH2CH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  129 CH2CH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  130 CH2CH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  131 CH2CH3 3-pyridyl 2-(aminosulfonyl)phenyl  132 CH2CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl  133 CH2CH3 3-pyridyl 1-pyrrolidinocarbonyl  134 CH2CH3 3-pyridyl 2-(methylsulfonyl)phenyl  135 CH2CH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  136 CH2CH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  137 CH2CH3 3-pyridyl 1-methyl-2-imidazolyl  138 CH2CH3 3-pyridyl 2-methyl-1-imidazolyl  139 CH2CH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  140 CH2CH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  141 CH2CH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  142 CH2CH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  143 CH2CH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  144 CH2CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl  145 CH2CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  146 CH2CH3 2-pyrimidyl 1-pyrrolidinocarbonyl  147 CH2CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl  148 CH2CH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  149 CH2CH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  150 CH2CH3 2-pyrimidyl 1-methyl-2-imidazolyl  151 CH2CH3 2-pyrimidyl 2-methyl-1-imidazolyl  152 CH2CH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  153 CH2CH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  154 CH2CH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  155 CH2CH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  156 CH2CH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  157 CH2CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl  158 CH2CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  159 CH2CH3 5-pyrimidyl 1-pyrrolidinocarbonyl  160 CH2CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl  161 CH2CH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  162 CH2CH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  163 CH2CH3 5-pyrimidyl 1-methyl-2-imidazolyl  164 CH2CH3 5-pyrimidyl 2-methyl-1-imidazolyl  165 CH2CH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  166 CH2CH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  167 CH2CH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  168 CH2CH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  169 CH2CH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  170 CH2CH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl  171 CH2CH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl  172 CH2CH3 2-Cl-phenyl 1-pyrrolidinocarbonyl  173 CH2CH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl  174 CH2CH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl  175 CH2CH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl  176 CH2CH3 2-Cl-phenyl 1-methyl-2-imidazolyl  177 CH2CH3 2-Cl-phenyl 2-methyl-1-imidazolyl  178 CH2CH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  179 CH2CH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  180 CH2CH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  181 CH2CH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  182 CH2CH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  183 CH2CH3 2-F-phenyl 2-(aminosulfonyl)phenyl  184 CH2CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl  185 CH2CH3 2-F-phenyl 1-pyrrolidinocarbonyl  186 CH2CH3 2-F-phenyl 2-(methylsulfonyl)phenyl  187 CH2CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  188 CH2CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  189 CH2CH3 2-F-phenyl 1-methyl-2-imidazolyl  190 CH2CH3 2-F-phenyl 2-methyl-1-imidazolyl  191 CH2CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  192 CH2CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  193 CH2CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  194 CH2CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  195 CH2CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  196 CH2CH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  197 CH2CH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  198 CH2CH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl  199 CH2CH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  200 CH2CH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  201 CH2CH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  202 CH2CH3 2,6-diF-phenyl 1-methyl-2-imidazolyl  203 CH2CH3 2,6-diF-phenyl 2-methyl-1-imidazolyl  204 CH2CH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  205 CH2CH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  206 CH2CH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  207 CH2CH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  208 CH2CH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  209 CF3 phenyl 2-(aminosulfonyl)phenyl  210 CF3 phenyl 2-(methylaminosulfonyl)phenyl  211 CF3 phenyl 1-pyrrolidinocarbonyl  212 CF3 phenyl 2-(methylsulfonyl)phenyl  213 CF3 phenyl 2-(N,N- dimethylaminomethyl)phenyl  214 CF3 phenyl 2-(N-pyrrolidinylmethyl)phenyl  215 CF3 phenyl 1-methyl-2-imidazolyl  216 CF3 phenyl 2-methyl-1-imidazolyl  217 CF3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl  218 CF3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  219 CF3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  220 CF3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  221 CF3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  222 CF3 2-pyridyl 2-(aminosulfonyl)phenyl  223 CF3 2-pyridyl 2-(methylaminosulfonyl)phenyl  224 CF3 2-pyridyl 1-pyrrolidinocarbonyl  225 CF3 2-pyridyl 2-(methylsulfonyl)phenyl  226 CF3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  227 CF3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  228 CF3 2-pyridyl 1-methyl-2-imidazolyl  229 CF3 2-pyridyl 2-methyl-1-imidazolyl  230 CF3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  231 CF3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  232 CF3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  233 CF3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  234 CF3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  235 CF3 3-pyridyl 2-(aminosulfonyl)phenyl  236 CF3 3-pyridyl 2-(methylaminosulfonyl)phenyl  237 CF3 3-pyridyl 1-pyrrolidinocarbonyl  238 CF3 3-pyridyl 2-(methylsulfonyl)phenyl  239 CF3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  240 CF3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  241 CF3 3-pyridyl 1-methyl-2-imidazolyl  242 CF3 3-pyridyl 2-methyl-1-imidazolyl  243 CF3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  244 CF3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  245 CF3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  246 CF3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  247 CF3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  248 CF3 2-pyrimidyl 2-(aminosulfonyl)phenyl  249 CF3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  250 CF3 2-pyrimidyl 1-pyrrolidinocarbonyl  251 CF3 2-pyrimidyl 2-(methylsulfonyl)phenyl  252 CF3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  253 CF3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  254 CF3 2-pyrimidyl 1-methyl-2-imidazolyl  255 CF3 2-pyrimidyl 2-methyl-1-imidazolyl  256 CF3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  257 CF3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  258 CF3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  259 CF3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  260 CF3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  261 CF3 5-pyrimidyl 2-(aminosulfonyl)phenyl  262 CF3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  263 CF3 5-pyrimidyl 1-pyrrolidinocarbonyl  264 CF3 5-pyrimidyl 2-(methylsulfonyl)phenyl  265 CF3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  266 CF3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  267 CF3 5-pyrimidyl 1-methyl-2-imidazolyl  268 CF3 5-pyrimidyl 2-methyl-1-imidazolyl  269 CF3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  270 CF3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  271 CF3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  272 CF3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  273 CF3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  274 CF3 2-Cl-phenyl 2-(aminosulfonyl)phenyl  275 CF3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl  276 CF3 2-Cl-phenyl 1-pyrrolidinocarbonyl  277 CF3 2-Cl-phenyl 2-(methylsulfonyl)phenyl  278 CF3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl  279 CF3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl  280 CF3 2-Cl-phenyl 1-methyl-2-imidazolyl  281 CF3 2-Cl-phenyl 2-methyl-1-imidazolyl  282 CF3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  283 CF3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  284 CF3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  285 CF3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  286 CF3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  287 CF3 2-F-phenyl 2-(aminosulfonyl)phenyl  288 CF3 2-F-phenyl 2-(methylaminosulfonyl)phenyl  289 CF3 2-F-phenyl 1-pyrrolidinocarbonyl  290 CF3 2-F-phenyl 2-(methylsulfonyl)phenyl  291 CF3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  292 CF3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  293 CF3 2-F-phenyl 1-methyl-2-imidazolyl  294 CF3 2-F-phenyl 2-methyl-1-imidazolyl  295 CF3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  296 CF3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  297 CF3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  298 CF3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  299 CF3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  300 CF3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  301 CF3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  302 CF3 2,6-diF-phenyl 1-pyrrolidinocarbonyl  303 CF3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  304 CF3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  305 CF3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  306 CF3 2,6-diF-phenyl 1-methyl-2-imidazolyl  307 CF3 2,6-diF-phenyl 2-methyl-1-imidazolyl  308 CF3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  309 CF3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  310 CF3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  311 CF3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  312 CF3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  313 SCH3 phenyl 2-(aminosulfonyl)phenyl  314 SCH3 phenyl 2-(methylaminosulfonyl)phenyl  315 SCH3 phenyl 1-pyrrolidinocarbonyl  316 SCH3 phenyl 2-(methylsulfonyl)phenyl  317 SCH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl  318 SCH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl  319 SCH3 phenyl 1-methyl-2-imidazolyl  320 SCH3 phenyl 2-methyl-1-imidazolyl  321 SCH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl  322 SCH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  323 SCH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  324 SCH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  325 SCH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  326 SCH3 2-pyridyl 2-(aminosulfonyl)phenyl  327 SCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl  328 SCH3 2-pyridyl 1-pyrrolidinocarbonyl  329 SCH3 2-pyridyl 2-(methylsulfonyl)phenyl  330 SCH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  331 SCH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  332 SCH3 2-pyridyl 1-methyl-2-imidazolyl  333 SCH3 2-pyridyl 2-methyl-1-imidazolyl  334 SCH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  335 SCH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  336 SCH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  337 SCH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  338 SCH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  339 SCH3 3-pyridyl 2-(aminosulfonyl)phenyl  340 SCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl  341 SCH3 3-pyridyl 1-pyrrolidinocarbonyl  342 SCH3 3-pyridyl 2-(methylsulfonyl)phenyl  343 SCH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  344 SCH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  345 SCH3 3-pyridyl 1-methyl-2-imidazolyl  346 SCH3 3-pyridyl 2-methyl-1-imidazolyl  347 SCH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  348 SCH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  349 SCH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  350 SCH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  351 SCH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  352 SCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl  353 SCH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  354 SCH3 2-pyrimidyl 1-pyrrolidinocarbonyl  355 SCH3 2-pyrimidyl 2-(methylsulfonyl)phenyl  356 SCH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  357 SCH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  358 SCH3 2-pyrimidyl 1-methyl-2-imidazolyl  359 SCH3 2-pyrimidyl 2-methyl-1-imidazolyl  360 SCH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  361 SCH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  362 SCH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  363 SCH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  364 SCH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  365 SCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl  366 SCH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  367 SCH3 5-pyrimidyl 1-pyrrolidinocarbonyl  368 SCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl  369 SCH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  370 SCH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  371 SCH3 5-pyrimidyl 1-methyl-2-imidazolyl  372 SCH3 5-pyrimidyl 2-methyl-1-imidazolyl  373 SCH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  374 SCH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  375 SCH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  376 SCH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  377 SCH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  378 SCH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl  379 SCH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl  380 SCH3 2-Cl-phenyl 1-pyrrolidinocarbonyl  381 SCH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl  382 SCH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl  383 SCH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl  384 SCH3 2-Cl-phenyl 1-methyl-2-imidazolyl  385 SCH3 2-Cl-phenyl 2-methyl-1-imidazolyl  386 SCH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  387 SCH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  388 SCH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  389 SCH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  390 SCH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  391 SCH3 2-F-phenyl 2-(aminosulfonyl)phenyl  392 SCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl  393 SCH3 2-F-phenyl 1-pyrrolidinocarbonyl  394 SCH3 2-F-phenyl 2-(methylsulfonyl)phenyl  395 SCH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  396 SCH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  397 SCH3 2-F-phenyl 1-methyl-2-imidazolyl  398 SCH3 2-F-phenyl 2-methyl-1-imidazolyl  399 SCH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  400 SCH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  401 SCH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  402 SCH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  403 SCH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  404 SCH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  405 SCH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  406 SCH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl  407 SCH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  408 SCH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  409 SCH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  410 SCH3 2,6-diF-phenyl 1-methyl-2-imidazolyl  411 SCH3 2,6-diF-phenyl 2-methyl-1-imidazolyl  412 SCH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  413 SCH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  414 SCH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  415 SCH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  416 SCH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  417 SOCH3 phenyl 2-(aminosulfonyl)phenyl  418 SOCH3 phenyl 2-(methylaminosulfonyl)phenyl  419 SOCH3 phenyl 1-pyrrolidinocarbonyl  420 SOCH3 phenyl 2-(methylsulfonyl)phenyl  421 SOCH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl  422 SOCH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl  423 SOCH3 phenyl 1-methyl-2-imidazolyl  424 SOCH3 phenyl 2-methyl-1-imidazolyl  425 SOCH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl  426 SOCH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  427 SOCH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  428 SOCH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  429 SOCH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  430 SOCH3 2-pyridyl 2-(aminosulfonyl)phenyl  431 SOCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl  432 SOCH3 2-pyridyl 1-pyrrolidinocarbonyl  433 SOCH3 2-pyridyl 2-(methylsulfonyl)phenyl  434 SOCH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  435 SOCH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  436 SOCH3 2-pyridyl 1-methyl-2-imidazolyl  437 SOCH3 2-pyridyl 2-methyl-i -imidazolyl  438 SOCH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  439 SOCH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  440 SOCH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  441 SOCH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  442 SOCH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  443 SOCH3 3-pyridyl 2-(aminosulfonyl)phenyl  444 SOCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl  445 SOCH3 3-pyridyl 1-pyrrolidinocarbonyl  446 SOCH3 3-pyridyl 2-(methylsulfonyl)phenyl  447 SOCH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  448 SOCH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  449 SOCH3 3-pyridyl 1-methyl-2-imidazolyl  450 SOCH3 3-pyridyl 2-methyl-1-imidazolyl  451 SOCH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  452 SOCH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  453 SOCH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  454 SOCH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  455 SOCH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  456 SOCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl  457 SOCH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  458 SOCH3 2-pyrimidyl 1-pyrrolidinocarbonyl  459 SOCH3 2-pyrimidyl 2-(methylsulfonyl)phenyl  460 SOCH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  461 SOCH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  462 SOCH3 2-pyrimidyl 1-methyl-2-imidazolyl  463 SOCH3 2-pyrimidyl 2-methyl-1-imidazolyl  464 SOCH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  465 SOCH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  466 SOCH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  467 SOCH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  468 SOCH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  469 SOCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl  470 SOCH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  471 SOCH3 5-pyrimidyl 1-pyrrolidinocarbonyl  472 SOCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl  473 SOCH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  474 SOCH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  475 SOCH3 5-pyrimidyl 1-methyl-2-imidazolyl  476 SOCH3 5-pyrimidyl 2-methyl-1-imidazolyl  477 SOCH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  478 SOCH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  479 SOCH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  480 SOCH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  481 SOCH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  482 SOCH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl  483 SOCH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl  484 SOCH3 2-Cl-phenyl 1-pyrrolidinocarbonyl  485 SOCH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl  486 SOCH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl  487 SOCH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl  488 SOCH3 2-Cl-phenyl 1-methyl-2-imidazolyl  489 SOCH3 2-Cl-phenyl 2-methyl-1-imidazolyl  490 SOCH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  491 SOCH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  492 SOCH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  493 SOCH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  494 SOCH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  495 SOCH3 2-F-phenyl 2-(aminosulfonyl)phenyl  496 SOCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl  497 SOCH3 2-F-phenyl 1-pyrrolidinocarbonyl  498 SOCH3 2-F-phenyl 2-(methylsulfonyl)phenyl  499 SOCH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  500 SOCH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  501 SOCH3 2-F-phenyl 1-methyl-2-imidazolyl  502 SOCH3 2-F-phenyl 2-methyl-1-imidazolyl  503 SOCH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  504 SOCH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  505 SOCH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  506 SOCH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  507 SOCH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  508 SOCH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  509 SOCH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  510 SOCH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl  511 SOCH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  512 SOCH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  513 SOCH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  514 SOCH3 2,6-diF-phenyl 1-methyl-2-imidazolyl  515 SOCH3 2,6-diF-phenyl 2-methyl-1-imidazolyl  516 SOCH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  517 SOCH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  518 SOCH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  519 SOCH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  520 SOCH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  521 SO2CH3 phenyl 2-(aminosulfonyl)phenyl  522 SO2CH3 phenyl 2-(methylaminosulfonyl)phenyl  523 SO2CH3 phenyl 1-pyrrolidinocarbonyl  524 SO2CH3 phenyl 2-(methylsulfonyl)phenyl  525 SO2CH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl  526 SO2CH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl  527 SO2CH3 phenyl 1-methyl-2-imidazolyl  528 SO2CH3 phenyl 2-methyl-1-imidazolyl  529 SO2CH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl  530 SO2CH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  531 SO2CH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  532 SO2CH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  533 SO2CH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  534 SO2CH3 2-pyridyl 2-(aminosulfonyl)phenyl  535 SO2CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl  536 SO2CH3 2-pyridyl 1-pyrrolidinocarbonyl  537 SO2CH3 2-pyridyl 2-(methylsulfonyl)phenyl  538 SO2CH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  539 SO2CH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  540 SO2CH3 2-pyridyl 1-methyl-2-imidazolyl  541 SO2CH3 2-pyridyl 2-methyl-1-imidazolyl  542 SO2CH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  543 SO2CH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  544 SO2CH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  545 SO2CH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  546 SO2CH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  547 SO2CH3 3-pyridyl 2-(aminosulfonyl)phenyl  548 SO2CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl  549 SO2CH3 3-pyridyl 1-pyrrolidinocarbonyl  550 SO2CH3 3-pyridyl 2-(methylsulfonyl)phenyl  551 SO2CH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  552 SO2CH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  553 SO2CH3 3-pyridyl 1-methyl-2-imidazolyl  554 SO2CH3 3-pyridyl 2-methyl-1-imidazolyl  555 SO2CH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  556 SO2CH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  557 SO2CH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  558 SO2CH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  559 SO2CH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  560 SO2CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl  561 SO2CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  562 SO2CH3 2-pyrimidyl 1-pyrrolidinocarbonyl  563 SO2CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl  564 SO2CH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  565 SO2CH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  566 SO2CH3 2-pyrimidyl 1-methyl-2-imidazolyl  567 SO2CH3 2-pyrimidyl 2-methyl-1-imidazolyl  568 SO2CH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  569 SO2CH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  570 SO2CH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  571 SO2CH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  572 SO2CH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  573 SO2CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl  574 SO2CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  575 SO2CH3 5-pyrimidyl 1-pyrrolidinocarbonyl  576 SO2CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl  577 SO2CH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  578 SO2CH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  579 SO2CH3 5-pyrimidyl 1-methyl-2-imidazolyl  580 SO2CH3 5-pyrimidyl 2-methyl-1-imidazolyl  581 SO2CH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  582 SO2CH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  583 SO2CH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  584 SO2CH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  585 SO2CH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  586 SO2CH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl  587 SO2CH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl  588 SO2CH3 2-Cl-phenyl 1-pyrrolidinocarbonyl  589 SO2CH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl  590 SO2CH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl  591 SO2CH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl  592 SO2CH3 2-Cl-phenyl 1-methyl-2-imidazolyl  593 SO2CH3 2-Cl-phenyl 2-methyl-1-imidazolyl  594 SO2CH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  595 SO2CH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  596 SO2CH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  597 SO2CH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  598 SO2CH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  599 SO2CH3 2-F-phenyl 2-(aminosulfonyl)phenyl  600 SO2CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl  601 SO2CH3 2-F-phenyl 1-pyrrolidinocarbonyl  602 SO2CH3 2-F-phenyl 2-(methylsulfonyl)phenyl  603 SO2CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  604 SO2CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  605 SO2CH3 2-F-phenyl 1-methyl-2-imidazolyl  606 SO2CH3 2-F-phenyl 2-methyl-1-imidazolyl  607 SO2CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  608 SO2CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  609 SO2CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  610 SO2CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  611 SO2CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  612 SO2CH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  613 SO2CH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  614 SO2CH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl  615 SO2CH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  616 SO2CH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  617 SO2CH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  618 SO2CH3 2,6-diF-phenyl 1-methyl-2-imidazolyl  619 SO2CH3 2,6-diF-phenyl 2-methyl-1-imidazolyl  620 SO2CH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  621 SO2CH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  622 SO2CH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  623 SO2CH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  624 SO2CH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  625 Cl phenyl 2-(aminosulfonyl)phenyl  626 Cl phenyl 2-(methylaminosulfonyl)phenyl  627 Cl phenyl 1-pyrrolidinocarbonyl  628 Cl phenyl 2-(methylsulfonyl)phenyl  629 Cl phenyl 2-(N,N- dimethylaminomethyl)phenyl  630 Cl phenyl 2-(N-pyrrolidinylmethyl)phenyl  631 Cl phenyl 1-methyl-2-imidazolyl  632 Cl phenyl 2-methyl-1-imidazolyl  633 Cl phenyl 2-(dimethylaminomethyl)-1- imidazolyl  634 Cl phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  635 Cl phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  636 Cl phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  637 Cl phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  638 Cl 2-pyridyl 2-(aminosulfonyl)phenyl  639 Cl 2-pyridyl 2-(methylaminosulfonyl)phenyl  640 Cl 2-pyridyl 1-pyrrolidinocarbonyl  641 Cl 2-pyridyl 2-(methylsulfonyl)phenyl  642 Cl 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  643 Cl 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  644 Cl 2-pyridyl 1-methyl-2-imidazolyl  645 Cl 2-pyridyl 2-methyl-1-imidazolyl  646 Cl 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  647 Cl 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  648 Cl 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  649 Cl 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  650 Cl 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  651 Cl 3-pyridyl 2-(aminosulfonyl)phenyl  652 Cl 3-pyridyl 2-(methylaminosulfonyl)phenyl  653 Cl 3-pyridyl 1-pyrrolidinocarbonyl  654 Cl 3-pyridyl 2-(methylsulfonyl)phenyl  655 Cl 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  656 Cl 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  657 Cl 3-pyridyl 1-methyl-2-imidazolyl  658 Cl 3-pyridyl 2-methyl-1-imidazolyl  659 Cl 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  660 Cl 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  661 Cl 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  662 Cl 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  663 Cl 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  664 Cl 2-pyrimidyl 2-(aminosulfonyl)phenyl  665 Cl 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  666 Cl 2-pyrimidyl 1-pyrrolidinocarbonyl  667 Cl 2-pyrimidyl 2-(methylsulfonyl)phenyl  668 Cl 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  669 Cl 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  670 Cl 2-pyrimidyl 1-methyl-2-imidazolyl  671 Cl 2-pyrimidyl 2-methyl-1-imidazolyl  672 Cl 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  673 Cl 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  674 Cl 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  675 Cl 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  676 Cl 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  677 Cl 5-pyrimidyl 2-(aminosulfonyl)phenyl  678 Cl 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  679 Cl 5-pyrimidyl 1-pyrrolidinocarbonyl  680 Cl 5-pyrimidyl 2-(methylsulfonyl)phenyl  681 Cl 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  682 Cl 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  683 Cl 5-pyrimidyl 1-methyl-2-imidazolyl  684 Cl 5-pyrimidyl 2-methyl-1-imidazolyl  685 Cl 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  686 Cl 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  687 Cl 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  688 Cl 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  689 Cl 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  690 Cl 2-Cl-phenyl 2-(aminosulfonyl)phenyl  691 Cl 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl  692 Cl 2-Cl-phenyl 1-pyrrolidinocarbonyl  693 Cl 2-Cl-phenyl 2-(methylsulfonyl)phenyl  694 Cl 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl  695 Cl 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl  696 Cl 2-Cl-phenyl 1-methyl-2-imidazolyl  697 Cl 2-Cl-phenyl 2-methyl-1-imidazolyl  698 Cl 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  699 Cl 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  700 Cl 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  701 Cl 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  702 Cl 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  703 Cl 2-F-phenyl 2-(aminosulfonyl)phenyl  704 Cl 2-F-phenyl 2-(methylaminosulfonyl)phenyl  705 Cl 2-F-phenyl 1-pyrrolidinocarbonyl  706 Cl 2-F-phenyl 2-(methylsulfonyl)phenyl  707 Cl 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  708 Cl 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  709 Cl 2-F-phenyl 1-methyl-2-imidazolyl  710 Cl 2-F-phenyl 2-methyl-1-imidazolyl  711 Cl 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  712 Cl 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  713 Cl 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  714 Cl 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  715 Cl 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  716 Cl 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  717 Cl 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  718 Cl 2,6-diF-phenyl 1-pyrrolidinocarbonyl  719 Cl 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  720 Cl 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  721 Cl 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  722 Cl 2,6-diF-phenyl 1-methyl-2-imidazolyl  723 Cl 2,6-diF-phenyl 2-methyl-1-imidazolyl  724 Cl 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  725 Cl 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  726 Cl 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  727 Cl 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  728 Cl 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  729 F phenyl 2-(aminosulfonyl)phenyl  730 F phenyl 2-(methylaminosulfonyl)phenyl  731 F phenyl 1-pyrrolidinocarbonyl  732 F phenyl 2-(methylsulfonyl)phenyl  733 F phenyl 2-(N,N- dimethylaminomethyl)phenyl  734 F phenyl 2-(N-pyrrolidinylmethyl)phenyl  735 F phenyl 1-methyl-2-imidazolyl  736 F phenyl 2-methyl-1-imidazolyl  737 F phenyl 2-(dimethylaminomethyl)-1- imidazolyl  738 F phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  739 F phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  740 F phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  741 F phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  742 F 2-pyridyl 2-(aminosulfonyl)phenyl  743 F 2-pyridyl 2-(methylaminosulfonyl)phenyl  744 F 2-pyridyl 1-pyrrolidinocarbonyl  745 F 2-pyridyl 2-(methylsulfonyl)phenyl  746 F 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  747 F 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  748 F 2-pyridyl 1-methyl-2-imidazolyl  749 F 2-pyridyl 2-methyl-1-imidazolyl  750 F 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  751 F 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  752 F 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  753 F 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  754 F 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  755 F 3-pyridyl 2-(aminosulfonyl)phenyl  756 F 3-pyridyl 2-(methylaminosulfonyl)phenyl  757 F 3-pyridyl 1-pyrrolidinocarbonyl  758 F 3-pyridyl 2-(methylsulfonyl)phenyl  759 F 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  760 F 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  761 F 3-pyridyl 1-methyl-2-imidazolyl  762 F 3-pyridyl 2-methyl-1-imidazolyl  763 F 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  764 F 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  765 F 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  766 F 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  767 F 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  768 F 2-pyrimidyl 2-(aminosulfonyl)phenyl  769 F 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  770 F 2-pyrimidyl 1-pyrrolidinocarbonyl  771 F 2-pyrimidyl 2-(methylsulfonyl)phenyl  772 F 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  773 F 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  774 F 2-pyrimidyl 1-methyl-2-imidazolyl  775 F 2-pyrimidyl 2-methyl-1-imidazolyl  776 F 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  777 F 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  778 F 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  779 F 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  780 F 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  781 F 5-pyrimidyl 2-(aminosulfonyl)phenyl  782 F 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  783 F 5-pyrimidyl 1-pyrrolidinocarbonyl  784 F 5-pyrimidyl 2-(methylsulfonyl)phenyl  785 F 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  786 F 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  787 F 5-pyrimidyl 1-methyl-2-imidazolyl  788 F 5-pyrimidyl 2-methyl-1-imidazolyl  789 F 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  790 F 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  791 F 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  792 F 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  793 F 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  794 F 2-F-phenyl 2-(aminosulfonyl)phenyl  795 F 2-F-phenyl 2-(methylaminosulfonyl)phenyl  796 F 2-F-phenyl 1-pyrrolidinocarbonyl  797 F 2-F-phenyl 2-(methylsulfonyl)phenyl  798 F 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  799 F 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  800 F 2-F-phenyl 1-methyl-2-imidazolyl  801 F 2-F-phenyl 2-methyl-1-imidazolyl  802 F 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  803 F 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  804 F 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  805 F 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  806 F 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  807 F 2-F-phenyl 2-(aminosulfonyl)phenyl  808 F 2-F-phenyl 2-(methylaminosulfonyl)phenyl  809 F 2-F-phenyl 1-pyrrolidinocarbonyl  810 F 2-F-phenyl 2-(methylsulfonyl)phenyl  811 F 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  812 F 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  813 F 2-F-phenyl 1-methyl-2-imidazolyl  814 F 2-F-phenyl 2-methyl-1-imidazolyl  815 F 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  816 F 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  817 F 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  818 F 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  819 F 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  820 F 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  821 F 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  822 F 2,6-diF-phenyl 1-pyrrolidinocarbonyl  823 F 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  824 F 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  825 F 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  826 F 2,6-diF-phenyl 1-methyl-2-imidazolyl  827 F 2,6-diF-phenyl 2-methyl-1-imidazolyl  828 F 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  829 F 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  830 F 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  831 F 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  832 F 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  833 CO2CH3 phenyl 2-(aminosulfonyl)phenyl  834 CO2CH3 phenyl 2-(methylaminosulfonyl)phenyl  835 CO2CH3 phenyl 1-pyrrolidinocarbonyl  836 CO2CH3 phenyl 2-(methylsulfonyl)phenyl  837 CO2CH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl  838 CO2CH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl  839 CO2CH3 phenyl 1-methyl-2-imidazolyl  840 CO2CH3 phenyl 2-methyl-1-imidazolyl  841 CO2CH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl  842 CO2CH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  843 CO2CH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  844 CO2CH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  845 CO2CH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  846 CO2CH3 2-pyridyl 2-(aminosulfonyl)phenyl  847 CO2CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl  848 CO2CH3 2-pyridyl 1-pyrrolidinocarbonyl  849 CO2CH3 2-pyridyl 2-(methylsulfonyl)phenyl  850 CO2CH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  851 CO2CH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  852 CO2CH3 2-pyridyl 1-methyl-2-imidazolyl  853 CO2CH3 2-pyridyl 2-methyl-1-imidazolyl  854 CO2CH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  855 CO2CH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  856 CO2CH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  857 CO2CH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  858 CO2CH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  859 CO2CH3 3-pyridyl 2-(aminosulfonyl)phenyl  860 CO2CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl  861 CO2CH3 3-pyridyl 1-pyrrolidinocarbonyl  862 CO2CH3 3-pyridyl 2-(methylsulfonyl)phenyl  863 CO2CH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  864 CO2CH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  865 CO2CH3 3-pyridyl 1-methyl-2-imidazolyl  866 CO2CH3 3-pyridyl 2-methyl-1-imidazolyl  867 CO2CH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  868 CO2CH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  869 CO2CH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  870 CO2CH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  871 CO2CH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  872 CO2CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl  873 CO2CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  874 CO2CH3 2-pyrimidyl 1-pyrrolidinocarbonyl  875 CO2CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl  876 CO2CH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  877 CO2CH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  878 CO2CH3 2-pyrimidyl 1-methyl-2-imidazolyl  879 CO2CH3 2-pyrimidyl 2-methyl-1-imidazolyl  880 CO2CH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  881 CO2CH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  882 CO2CH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  883 CO2CH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  884 CO2CH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  885 CO2CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl  886 CO2CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  887 CO2CH3 5-pyrimidyl 1-pyrrolidinocarbonyl  888 CO2CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl  889 CO2CH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  890 CO2CH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  891 CO2CH3 5-pyrimidyl 1-methyl-2-imidazolyl  892 CO2CH3 5-pyrimidyl 2-methyl-1-imidazolyl  893 CO2CH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  894 CO2CH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  895 CO2CH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  896 CO2CH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  897 CO2CH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  898 CO2CH3 2-F-phenyl 2-(aminosulfonyl)phenyl  899 CO2CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl  900 CO2CH3 2-F-phenyl 1-pyrrolidinocarbonyl  901 CO2CH3 2-F-phenyl 2-(methylsulfonyl)phenyl  902 CO2CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  903 CO2CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  904 CO2CH3 2-F-phenyl 1-methyl-2-imidazolyl  905 CO2CH3 2-F-phenyl 2-methyl-1-imidazolyl  906 CO2CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  907 CO2CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  908 CO2CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  909 CO2CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  910 CO2CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  911 CO2CH3 2-F-phenyl 2-(aminosulfonyl)phenyl  912 CO2CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl  913 CO2CH3 2-F-phenyl 1-pyrrolidinocarbonyl  914 CO2CH3 2-F-phenyl 2-(methylsulfonyl)phenyl  915 CO2CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl  916 CO2CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl  917 CO2CH3 2-F-phenyl 1-methyl-2-imidazolyl  918 CO2CH3 2-F-phenyl 2-methyl-1-imidazolyl  919 CO2CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  920 CO2CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  921 CO2CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  922 CO2CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  923 CO2CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  924 CO2CH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl  925 CO2CH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl  926 CO2CH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl  927 CO2CH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl  928 CO2CH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl  929 CO2CH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl  930 CO2CH3 2,6-diF-phenyl 1-methyl-2-imidazolyl  931 CO2CH3 2,6-diF-phenyl 2-methyl-1-imidazolyl  932 CO2CH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl  933 CO2CH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  934 CO2CH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  935 CO2CH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  936 CO2CH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  937 CH2OCH3 phenyl 2-(aminosulfonyl)phenyl  938 CH2OCH3 phenyl 2-(methylaminosulfonyl)phenyl  939 CH2OCH3 phenyl 1-pyrrolidinocarbonyl  940 CH2OCH3 phenyl 2-(methylsulfonyl)phenyl  941 CH2OCH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl  942 CH2OCH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl  943 CH2OCH3 phenyl 1-methyl-2-imidazolyl  944 CH2OCH3 phenyl 2-methyl-1-imidazolyl  945 CH2OCH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl  946 CH2OCH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  947 CH2OCH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  948 CH2OCH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  949 CH2OCH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  950 CH2OCH3 2-pyridyl 2-(aminosulfonyl)phenyl  951 CH2OCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl  952 CH2OCH3 2-pyridyl 1-pyrrolidinocarbonyl  953 CH2OCH3 2-pyridyl 2-(methylsulfonyl)phenyl  954 CH2OCH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  955 CH2OCH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  956 CH2OCH3 2-pyridyl 1-methyl-2-imidazolyl  957 CH2OCH3 2-pyridyl 2-methyl-1-imidazolyl  958 CH2OCH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  959 CH2OCH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  960 CH2OCH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  961 CH2OCH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  962 CH2OCH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  963 CH2OCH3 3-pyridyl 2-(aminosulfonyl)phenyl  964 CH2OCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl  965 CH2OCH3 3-pyridyl 1-pyrrolidinocarbonyl  966 CH2OCH3 3-pyridyl 2-(methylsulfonyl)phenyl  967 CH2OCH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl  968 CH2OCH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl  969 CH2OCH3 3-pyridyl 1-methyl-2-imidazolyl  970 CH2OCH3 3-pyridyl 2-methyl-1-imidazolyl  971 CH2OCH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl  972 CH2OCH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  973 CH2OCH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  974 CH2OCH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  975 CH2OCH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  976 CH2OCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl  977 CH2OCH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl  978 CH2OCH3 2-pyrimidyl 1-pyrrolidinocarbonyl  979 CH2OCH3 2-pyrimidyl 2-(methylsulfonyl)phenyl  980 CH2OCH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  981 CH2OCH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  982 CH2OCH3 2-pyrimidyl 1-methyl-2-imidazolyl  983 CH2OCH3 2-pyrimidyl 2-methyl-1-imidazolyl  984 CH2OCH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  985 CH2OCH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  986 CH2OCH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl  987 CH2OCH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl  988 CH2OCH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl  989 CH2OCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl  990 CH2OCH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl  991 CH2OCH3 5-pyrimidyl 1-pyrrolidinocarbonyl  992 CH2OCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl  993 CH2OCH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl  994 CH2OCH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl  995 CH2OCH3 5-pyrimidyl 1-methyl-2-imidazolyl  996 CH2OCH3 5-pyrimidyl 2-methyl-1-imidazolyl  997 CH2OCH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl  998 CH2OCH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl  999 CH2OCH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1000 CH2OCH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1001 CH2OCH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1002 CH2OCH3 2-F-phenyl 2-(aminosulfonyl)phenyl 1003 CH2OCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1004 CH2OCH3 2-F-phenyl 1-pyrrolidinocarbonyl 1005 CH2OCH3 2-F-phenyl 2-(methylsulfonyl)phenyl 1006 CH2OCH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1007 CH2OCH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1008 CH2OCH3 2-F-phenyl 1-methyl-2-imidazolyl 1009 CH2OCH3 2-F-phenyl 2-methyl-1-imidazolyl 1010 CH2OCH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1011 CH2OCH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1012 CH2OCH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1013 CH2OCH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1014 CH2OCH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1015 CH2OCH3 2-F-phenyl 2-(aminosulfonyl)phenyl 1016 CH2OCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1017 CH2OCH3 2-F-phenyl 1-pyrrolidinocarbonyl 1018 CH2OCH3 2-F-phenyl 2-(methylsulfonyl)phenyl 1019 CH2OCH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1020 CH2OCH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1021 CH2OCH3 2-F-phenyl 1-methyl-2-imidazolyl 1022 CH2OCH3 2-F-phenyl 2-methyl-1-imidazolyl 1023 CH2OCH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1024 CH2OCH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1025 CH2OCH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1026 CH2OCH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1027 CH2OCH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1028 CH2OCH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 1029 CH2OCH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 1030 CH2OCH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 1031 CH2OCH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 1032 CH2OCH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1033 CH2OCH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1034 CH2OCH3 2,6-diF-phenyl 1-methyl-2-imidazolyl 1035 CH2OCH3 2,6-diF-phenyl 2-methyl-1-imidazolyl 1036 CH2OCH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1037 CH2OCH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1038 CH2OCH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1039 CH2OCH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1040 CH2OCH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1041 CONH2 phenyl 2-(aminosulfonyl)phenyl 1042 CONH2 phenyl 2-(methylaminosulfonyl)phenyl 1043 CONH2 phenyl 1-pyrrolidinocarbonyl 1044 CONH2 phenyl 2-(methylsulfonyl)phenyl 1045 CONH2 phenyl 2-(N,N- dimethylaminomethyl)phenyl 1046 CONH2 phenyl 2-(N-pyrrolidinylmethyl)phenyl 1047 CONH2 phenyl 1-methyl-2-imidazolyl 1048 CONH2 phenyl 2-methyl-1-imidazolyl 1049 CONH2 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1050 CONH2 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1051 CONH2 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1052 CONH2 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1053 CONH2 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1054 CONH2 2-pyridyl 2-(aminosulfonyl)phenyl 1055 CONH2 2-pyridyl 2-(methylaminosulfonyl)phenyl 1056 CONH2 2-pyridyl 1-pyrrolidinocarbonyl 1057 CONH2 2-pyridyl 2-(methylsulfonyl)phenyl 1058 CONH2 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1059 CONH2 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1060 CONH2 2-pyridyl 1-methyl-2-imidazolyl 1061 CONH2 2-pyridyl 2-methyl-1-imidazolyl 1062 CONH2 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1063 CONH2 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1064 CONH2 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1065 CONH2 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1066 CONH2 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1067 CONH2 3-pyridyl 2-(aminosulfonyl)phenyl 1068 CONH2 3-pyridyl 2-(methylaminosulfonyl)phenyl 1069 CONH2 3-pyridyl 1-pyrrolidinocarbonyl 1070 CONH2 3-pyridyl 2-(methylsulfonyl)phenyl 1071 CONH2 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1072 CONH2 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1073 CONH2 3-pyridyl 1-methyl-2-imidazolyl 1074 CONH2 3-pyridyl 2-methyl-1-imidazolyl 1075 CONH2 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1076 CONH2 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1077 CONH2 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1078 CONH2 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1079 CONH2 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1080 CONH2 2-pyrimidyl 2-(aminosulfonyl)phenyl 1081 CONH2 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1082 CONH2 2-pyrimidyl 1-pyrrolidinocarbonyl 1083 CONH2 2-pyrimidyl 2-(methylsulfonyl)phenyl 1084 CONH2 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1085 CONH2 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1086 CONH2 2-pyrimidyl 1-methyl-2-imidazolyl 1087 CONH2 2-pyrimidyl 2-methyl-1-imidazolyl 1088 CONH2 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1089 CONH2 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1090 CONH2 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1091 CONH2 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1092 CONH2 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1093 CONH2 5-pyrimidyl 2-(aminosulfonyl)phenyl 1094 CONH2 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 1095 CONH2 5-pyrimidyl 1-pyrrolidinocarbonyl 1096 CONH2 5-pyrimidyl 2-(methylsulfonyl)phenyl 1097 CONH2 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1098 CONH2 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1099 CONH2 5-pyrimidyl 1-methyl-2-imidazolyl 1100 CONH2 5-pyrimidyl 2-methyl-1-imidazolyl 1101 CONH2 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1102 CONH2 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1103 CONH2 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1104 CONH2 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1105 CONH2 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1106 CONH2 2-F-phenyl 2-(aminosulfonyl)phenyl 1107 CONH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1108 CONH2 2-F-phenyl 1-pyrrolidinocarbonyl 1109 CONH2 2-F-phenyl 2-(methylsulfonyl)phenyl 1110 CONH2 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1111 CONH2 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1112 CONH2 2-F-phenyl 1-methyl-2-imidazolyl 1113 CONH2 2-F-phenyl 2-methyl-1-imidazolyl 1114 CONH2 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1115 CONH2 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1116 CONH2 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1117 CONH2 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1118 CONH2 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1119 CONH2 2-F-phenyl 2-(aminosulfonyl)phenyl 1120 CONH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1121 CONH2 2-F-phenyl 1-pyrrolidinocarbonyl 1122 CONH2 2-F-phenyl 2-(methylsulfonyl)phenyl 1123 CONH2 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1124 CONH2 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1125 CONH2 2-F-phenyl 1-methyl-2-imidazolyl 1126 CONH2 2-F-phenyl 2-methyl-1-imidazolyl 1127 CONH2 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1128 CONH2 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1129 CONH2 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1130 CONH2 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1131 CONH2 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1132 CONH2 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 1133 CONH2 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 1134 CONH2 2,6-diF-phenyl 1-pyrrolidinocarbonyl 1135 CONH2 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 1136 CONH2 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1137 CONH2 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1138 CONH2 2,6-diF-phenyl 1-methyl-2-imidazolyl 1139 CONH2 2,6-diF-phenyl 2-methyl-1-imidazolyl 1140 CONH2 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1141 CONH2 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1142 CONH2 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1143 CONH2 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1144 CONH2 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1145 CN phenyl 2-(aminosulfonyl)phenyl 1146 CN phenyl 2-(methylaminosulfonyl)phenyl 1147 CN phenyl 1-pyrrolidinocarbonyl 1148 CN phenyl 2-(methylsulfonyl)phenyl 1149 CN phenyl 2-(N,N- dimethylaminomethyl)phenyl 1150 CN phenyl 2-(N-pyrrolidinylmethyl)phenyl 1151 CN phenyl 1-methyl-2-imidazolyl 1152 CN phenyl 2-methyl-1-imidazolyl 1153 CN phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1154 CN phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1155 CN phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1156 CN phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1157 CN phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1158 CN 2-pyridyl 2-(aminosulfonyl)phenyl 1159 CN 2-pyridyl 2-(methylaminosulfonyl)phenyl 1160 CN 2-pyridyl 1-pyrrolidinocarbonyl 1161 CN 2-pyridyl 2-(methylsulfonyl)phenyl 1162 CN 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1163 CN 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1164 CN 2-pyridyl 1-methyl-2-imidazolyl 1165 CN 2-pyridyl 2-methyl-1-imidazolyl 1166 CN 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1167 CN 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1168 CN 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1169 CN 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1170 CN 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1171 CN 3-pyridyl 2-(aminosulfonyl)phenyl 1172 CN 3-pyridyl 2-(methylaminosulfonyl)phenyl 1173 CN 3-pyridyl 1-pyrrolidinocarbonyl 1174 CN 3-pyridyl 2-(methylsulfonyl)phenyl 1175 CN 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1176 CN 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1177 CN 3-pyridyl 1-methyl-2-imidazolyl 1178 CN 3-pyridyl 2-methyl-1-imidazolyl 1179 CN 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1180 CN 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1181 CN 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1182 CN 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1183 CN 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1184 CN 2-pyrimidyl 2-(aminosulfonyl)phenyl 1185 CN 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1186 CN 2-pyrimidyl 1-pyrrolidinocarbonyl 1187 CN 2-pyrimidyl 2-(methylsulfonyl)phenyl 1188 CN 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1189 CN 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1190 CN 2-pyrimidyl 1-methyl-2-imidazolyl 1191 CN 2-pyrimidyl 2-methyl-1-imidazolyl 1192 CN 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1193 CN 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1194 CN 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1195 CN 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1196 CN 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1197 CN 5-pyrimidyl 2-(aminosulfonyl)phenyl 1198 CN 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 1199 CN 5-pyrimidyl 1-pyrrolidinocarbonyl 1200 CN 5-pyrimidyl 2-(methylsulfonyl)phenyl 1201 CN 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1202 CN 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1203 CN 5-pyrimidyl 1-methyl-2-imidazolyl 1204 CN 5-pyrimidyl 2-methyl-1-imidazolyl 1205 CN 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1206 CN 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1207 CN 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1208 CN 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1209 CN 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1210 CN 2-F-phenyl 2-(aminosulfonyl)phenyl 1211 CN 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1212 CN 2-F-phenyl 1-pyrrolidinocarbonyl 1213 CN 2-F-phenyl 2-(methylsulfonyl)phenyl 1214 CN 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1215 CN 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1216 CN 2-F-phenyl 1-methyl-2-imidazolyl 1217 CN 2-F-phenyl 2-methyl-1-imidazolyl 1218 CN 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1219 CN 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1220 CN 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1221 CN 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1222 CN 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1223 CN 2-F-phenyl 2-(aminosulfonyl)phenyl 1224 CN 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1225 CN 2-F-phenyl 1-pyrrolidinocarbonyl 1226 CN 2-F-phenyl 2-(methylsulfonyl)phenyl 1227 CN 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1228 CN 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1229 CN 2-F-phenyl 1-methyl-2-imidazolyl 1230 CN 2-F-phenyl 2-methyl-1-imidazolyl 1231 CN 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1232 CN 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1233 CN 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1234 CN 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1235 CN 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1236 CN 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 1237 CN 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 1238 CN 2,6-diF-phenyl 1-pyrrolidinocarbonyl 1239 CN 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 1240 CN 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1241 CN 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1242 CN 2,6-diF-phenyl 1-methyl-2-imidazolyl 1243 CN 2,6-diF-phenyl 2-methyl-1-imidazolyl 1244 CN 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1245 CN 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1246 CN 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1247 CN 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1248 CN 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1249 CH2NH2 phenyl 2-(aminosulfonyl)phenyl 1250 CH2NH2 phenyl 2-(methylaminosulfonyl)phenyl 1251 CH2NH2 phenyl 1-pyrrolidinocarbonyl 1252 CH2NH2 phenyl 2-(methylsulfonyl)phenyl 1253 CH2NH2 phenyl 2-(N,N- dimethylaminomethyl)phenyl 1254 CH2NH2 phenyl 2-(N-pyrrolidinylmethyl)phenyl 1255 CH2NH2 phenyl 1-methyl-2-imidazolyl 1256 CH2NH2 phenyl 2-methyl-1-imidazolyl 1257 CH2NH2 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1258 CH2NH2 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1259 CH2NH2 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1260 CH2NH2 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1261 CH2NH2 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1262 CH2NH2 2-pyridyl 2-(aminosulfonyl)phenyl 1263 CH2NH2 2-pyridyl 2-(methylaminosulfonyl)phenyl 1264 CH2NH2 2-pyridyl 1-pyrrolidinocarbonyl 1265 CH2NH2 2-pyridyl 2-(methylsulfonyl)phenyl 1266 CH2NH2 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1267 CH2NH2 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1268 CH2NH2 2-pyridyl 1-methyl-2-imidazolyl 1269 CH2NH2 2-pyridyl 2-methyl-1-imidazolyl 1270 CH2NH2 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1271 CH2NH2 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1272 CH2NH2 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1273 CH2NH2 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1274 CH2NH2 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1275 CH2NH2 3-pyridyl 2-(aminosulfonyl)phenyl 1276 CH2NH2 3-pyridyl 2-(methylaminosulfonyl)phenyl 1277 CH2NH2 3-pyridyl 1-pyrrolidinocarbonyl 1278 CH2NH2 3-pyridyl 2-(methylsulfonyl)phenyl 1279 CH2NH2 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1280 CH2NH2 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1281 CH2NH2 3-pyridyl 1-methyl-2-imidazolyl 1282 CH2NH2 3-pyridyl 2-methyl-1-imidazolyl 1283 CH2NH2 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1284 CH2NH2 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1285 CH2NH2 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1286 CH2NH2 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1287 CH2NH2 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1288 CH2NH2 2-pyrimidyl 2-(aminosulfonyl)phenyl 1289 CH2NH2 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1290 CH2NH2 2-pyrimidyl 1-pyrrolidinocarbonyl 1291 CH2NH2 2-pyrimidyl 2-(methylsulfonyl)phenyl 1292 CH2NH2 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1293 CH2NH2 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1294 CH2NH2 2-pyrimidyl 1-methyl-2-imidazolyl 1295 CH2NH2 2-pyrimidyl 2-methyl-1-imidazolyl 1296 CH2NH2 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1297 CH2NH2 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1298 CH2NH2 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1299 CH2NH2 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1300 CH2NH2 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1301 CH2NH2 5-pyrimidyl 2-(aminosulfonyl)phenyl 1302 CH2NH2 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 1303 CH2NH2 5-pyrimidyl 1-pyrrolidinocarbonyl 1304 CH2NH2 5-pyrimidyl 2-(methylsulfonyl)phenyl 1305 CH2NH2 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1306 CH2NH2 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1307 CH2NH2 5-pyrimidyl 1-methyl-2-imidazolyl 1308 CH2NH2 5-pyrimidyl 2-methyl-1-imidazolyl 1309 CH2NH2 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1310 CH2NH2 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1311 CH2NH2 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1312 CH2NH2 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1313 CH2NH2 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1314 CH2NH2 2-F-phenyl 2-(aminosulfonyl)phenyl 1315 CH2NH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1316 CH2NH2 2-F-phenyl 1-pyrrolidinocarbonyl 1317 CH2NH2 2-F-phenyl 2-(methylsulfonyl)phenyl 1318 CH2NH2 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1319 CH2NH2 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1320 CH2NH2 2-F-phenyl 1-methyl-2-imidazolyl 1321 CH2NH2 2-F-phenyl 2-methyl-1-imidazolyl 1322 CH2NH2 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1323 CH2NH2 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1324 CH2NH2 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1325 CH2NH2 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1326 CH2NH2 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1327 CH2NH2 2-F-phenyl 2-(aminosulfonyl)phenyl 1328 CH2NH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1329 CH2NH2 2-F-phenyl 1-pyrrolidinocarbonyl 1330 CH2NH2 2-F-phenyl 2-(methylsulfonyl)phenyl 1331 CH2NH2 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1332 CH2NH2 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1333 CH2NH2 2-F-phenyl 1-methyl-2-imidazolyl 1334 CH2NH2 2-F-phenyl 2-methyl-1-imidazolyl 1335 CH2NH2 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1336 CH2NH2 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1337 CH2NH2 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1338 CH2NH2 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1339 CH2NH2 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1340 CH2NH2 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 1341 CH2NH2 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 1342 CH2NH2 2,6-diF-phenyl 1-pyrrolidinocarbonyl 1343 CH2NH2 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 1344 CH2NH2 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1345 CH2NH2 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1346 CH2NH2 2,6-diF-phenyl 1-methyl-2-imidazolyl 1347 CH2NH2 2,6-diF-phenyl 2-methyl-1-imidazolyl 1348 CH2NH2 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1349 CH2NH2 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1350 CH2NH2 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1351 CH2NH2 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1352 CH2NH2 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1353 CH2NH— phenyl 2-(aminosulfonyl)phenyl SO2CH3 1354 CH2NH— phenyl 2-(methylaminosulfonyl)phenyl SO2CH3 1355 CH2NH— phenyl 1-pyrrolidinocarbonyl SO2CH3 1356 CH2NH— phenyl 2-(methylsulfonyl)phenyl SO2CH3 1357 CH2NH— phenyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1358 CH2NH— phenyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1359 CH2NH— phenyl 1-methyl-2-imidazolyl SO2CH3 1360 CH2NH— phenyl 2-methyl-1-imidazolyl SO2CH3 1361 CH2NH— phenyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1362 CH2NH— phenyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1363 CH2NH— phenyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1364 CH2NH— phenyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1365 CH2NH— phenyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1366 CH2NH— 2-pyridyl 2-(aminosulfonyl)phenyl SO2CH3 1367 CH2NH— 2-pyridyl 2-(methylaminosulfonyl)phenyl SO2CH3 1368 CH2NH— 2-pyridyl 1-pyrrolidinocarbonyl SO2CH3 1369 CH2NH— 2-pyridyl 2-(methylsulfonyl)phenyl SO2CH3 1370 CH2NH— 2-pyridyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl SO2CH3 1371 CH2NH— 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1372 CH2NH— 2-pyridyl 1-methyl-2-imidazolyl SO2CH3 1373 CH2NH— 2-pyridyl 2-methyl-1-imidazolyl SO2CH3 1374 CH2NH— 2-pyridyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1375 CH2NH— 2-pyridyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1376 CH2NH— 2-pyridyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1377 CH2NH— 2-pyridyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1378 CH2NH— 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1379 CH2NH— 3-pyridyl 2-(aminosulfonyl)phenyl SO2CH3 1380 CH2NH— 3-pyridyl 2-(methylaminosulfonyl)phenyl SO2CH3 1381 CH2NH- 3-pyridyl 1-pyrrolidinocarbonyl SO2CH3 1382 CH2NH— 3-pyridyl 2-(methylsulfonyl)phenyl SO2CH3 1383 CH2NH— 3-pyridyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1384 CH2NH— 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1385 CH2NH— 3-pyridyl 1-methyl-2-imidazolyl SO2CH3 1386 CH2NH— 3-pyridyl 2-methyl-1-imidazolyl SO2CH3 1387 CH2NH— 3-pyridyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1388 CH2NH— 3-pyridyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1389 CH2NH— 3-pyridyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1390 CH2NH— 3-pyridyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1391 CH2NH— 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1392 CH2NH— 2-pyrimidyl 2-(aminosulfonyl)phenyl SO2CH3 1393 CH2NH— 2-pyrimidyl 2-(methylaminosulfonyl)phenyl SO2CH3 1394 CH2NH— 2-pyrimidyl 1-pyrrolidinocarbonyl SO2CH3 1395 CH2NH— 2-pyrimidyl 2-(methylsulfonyl)phenyl SO2CH3 1396 CH2NH— 2-pyrimidyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1397 CH2NH— 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1398 CH2NH— 2-pyrimidyl 1-methyl-2-imidazolyl SO2CH3 1399 CH2NH— 2-pyrimidyl 2-methyl-1-imidazolyl SO2CH3 1400 CH2NH— 2-pyrimidyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1401 CH2NH— 2-pyrimidyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1402 CH2NH— 2-pyrimidyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1403 CH2NH— 2-pyrimidyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1404 CH2NH— 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1405 CH2NH— 5-pyrimidyl 2-(aminosulfonyl)phenyl SO2CH3 1406 CH2NH— 5-pyrimidyl 2-(methylaminosulfonyl)phenyl SO2CH3 1407 CH2NH— 5-pyrimidyl 1-pyrrolidinocarbonyl SO2CH3 1408 CH2NH— 5-pyrimidyl 2-(methylsulfonyl)phenyl SO2CH3 1409 CH2NH— 5-pyrimidyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1410 CH2NH— 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1411 CH2NH— 5-pyrimidyl 1-methyl-2-imidazolyl SO2CH3 1412 CH2NH— 5-pyrimidyl 2-methyl-1-imidazolyl SO2CH3 1413 CH2NH— 5-pyrimidyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1414 CH2NH— 5-pyrimidyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1415 CH2NH— 5-pyrimidyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1416 CH2NH— 5-pyrimidyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1417 CH2NH— 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1418 CH2NH— 2-Cl-phenyl 2-(aminosulfonyl)phenyl SO2CH3 1419 CH2NH— 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl SO2CH3 1420 CH2NH— 2-Cl-phenyl 1-pyrrolidinocarbonyl SO2CH3 1421 CH2NH— 2-Cl-phenyl 2-(methylsulfonyl)phenyl SO2CH3 1422 CH2NH— 2-Cl-phenyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1423 CH2NH— 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1424 CH2NH— 2-Cl-phenyl 1-methyl-2-imidazolyl SO2CH3 1425 CH2NH— 2-Cl-phenyl 2-methyl-1-imidazolyl SO2CH3 1426 CH2NH— 2-Cl-phenyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1427 CH2NH— 2-Cl-phenyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1428 CH2NH— 2-Cl-phenyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1429 CH2NH— 2-Cl-phenyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1430 CH2NH— 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl) SO2CH3 methyl)phenyl 1431 CH2NH— 2-F-phenyl 2-(aminosulfonyl)phenyl SO2CH3 1432 CH2NH— 2-F-phenyl 2-(methylaminosulfonyl)phenyl SO2CH3 1433 CH2NH— 2-F-phenyl 1-pyrrolidinocarbonyl SO2CH3 1434 CH2NH— 2-F-phenyl 2-(methylsulfonyl)phenyl SO2CH3 1435 CH2NH— 2-F-phenyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1436 CH2NH— 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1437 CH2NH— 2-F-phenyl 1-methyl-2-imidazolyl SO2CH3 1438 CH2NH— 2-F-phenyl 2-methyl-1-imidazolyl SO2CH3 1439 CH2NH— 2-F-phenyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1440 CH2NH— 2-F-phenyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1441 CH2NH— 2-F-phenyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1442 CH2NH— 2-F-phenyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1443 CH2NH— 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1444 CH2NH— 2,6-diF-phenyl 2-(aminosulfonyl)phenyl SO2CH3 1445 CH2NH— 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl SO2CH3 1446 CH2NH— 2,6-diF-phenyl 1-pyrrolidinocarbonyl SO2CH3 1447 CH2NH— 2,6-diF-phenyl 2-(methylsulfonyl)phenyl SO2CH3 1448 CH2NH— 2,6-diF-phenyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1449 CH2NH— 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1450 CH2NH— 2,6-diF-phenyl 1-methyl-2-imidazolyl SO2CH3 1451 CH2NH— 2,6-diF-phenyl 2-methyl-1-imidazolyl SO2CH3 1452 CH2NH— 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1453 CH2NH— 2,6-diF-phenyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1454 CH2NH— 2,6-diF-phenyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1455 CH2NH— 2,6-diF-phenyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1456 CH2NH— 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl Z is C(O)NH or C(O)CH₂

TABLE 2

Z is C(O)NH or C(O)CH₂ Ex# A B 1 phenyl 2-(aminosulfonyl)phenyl 2 phenyl 2-(methylaminosulfonyl)phenyl 3 phenyl 1-pyrrolidinocarbonyl 4 phenyl 2-(methylsulfonyl)phenyl 5 phenyl 2-(N,N- dimethylaminomethyl)phenyl 6 phenyl 2-(N-pyrrolidinylmethyl)phenyl 7 phenyl 1-methyl-2-imidazolyl 8 phenyl 2-methyl-1-imidazolyl 9 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 10 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 11 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 12 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 13 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 14 2-pyridyl 2-(aminosulfonyl)phenyl 15 2-pyridyl 2-(methylaminosulfonyl)phenyl 16 2-pyridyl 1-pyrrolidinocarbonyl 17 2-pyridyl 2-(methylsulfonyl)phenyl 18 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 19 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 20 2-pyridyl 1-methyl-2-imidazolyl 21 2-pyridyl 2-methyl-1-imidazolyl 22 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 23 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 24 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 25 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 26 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 27 3-pyridyl 2-(aminosulfonyl)phenyl 28 3-pyridyl 2-(methylaminosulfonyl)phenyl 29 3-pyridyl 1-pyrrolidinocarbonyl 30 3-pyridyl 2-(methylsulfonyl)phenyl 31 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 32 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 33 3-pyridyl 1-methyl-2-imidazolyl 34 3-pyridyl 2-methyl-1-imidazolyl 35 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 36 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 37 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 38 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 39 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 40 2-pyrimidyl 2-(aminosulfonyl)phenyl 41 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 42 2-pyrimidyl 1-pyrrolidinocarbonyl 43 2-pyrimidyl 2-(methylsulfonyl)phenyl 44 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 45 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 46 2-pyrimidyl 1-methyl-2-imidazolyl 47 2-pyrimidyl 2-methyl-1-imidazolyl 48 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 49 2-pyrimidyl 2-(N-(cyclopropyl methyl)aminomethyl)phenyl 50 2-pyrimidyl 2-(N-(cyclobutyl) aminomethyl)phenyl 51 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 52 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 53 5-pyrimidyl 2-(aminosulfonyl)phenyl 54 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 55 5-pyrimidyl 1-pyrrolidinocarbonyl 56 5-pyrimidyl 2-(methylsulfonyl)phenyl 57 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 58 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 59 5-pyrimidyl 1-methyl-2-imidazolyl 60 5-pyrimidyl 2-methyl-1-imidazolyl 61 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 62 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 63 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 64 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 65 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 66 2-Cl-phenyl 2-(aminosulfonyl)phenyl 67 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 68 2-Cl-phenyl 1-pyrrolidinocarbonyl 69 2-Cl-phenyl 2-(methylsulfonyl)phenyl 70 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 71 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 72 2-Cl-phenyl 1-methyl-2-imidazolyl 73 2-Cl-phenyl 2-methyl-1-imidazolyl 74 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 75 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 76 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 77 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 78 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 79 2-F-phenyl 2-(aminosulfonyl)phenyl 80 2-F-phenyl 2-(methylaminosulfonyl)phenyl 81 2-F-phenyl 1-pyrrolidinocarbonyl 82 2-F-phenyl 2-(methylsulfonyl)phenyl 83 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 84 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 85 2-F-phenyl 1-methyl-2-imidazolyl 86 2-F-phenyl 2-methyl-1-imidazolyl 87 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 88 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 89 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 90 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 91 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 92 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 93 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 94 2,6-diF-phenyl 1-pyrrolidinocarbonyl 95 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 96 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 97 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 98 2,6-diF-phenyl 1-methyl-2-imidazolyl 99 2,6-diF-phenyl 2-methyl-1-imidazolyl 100 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 101 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 102 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 103 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 104 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl

Obviously, numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise that as specifically described herein. 

What is claimed is:
 1. A compound of formula I:

ring D is selected from —(CH₂)₃—, —CH₂CH═CH—, —CH₂N═CH—, and a 5 membered aromatic system containing from 0-2 heteroatoms selected from the group N, O, and S, provided that from 0-1 O and S atoms are present; ring D is substituted with 0-2 R, provided that when ring D is unsubstituted, it contains at least one heteroatom; E is phenyl substituted with 0-1 R; R is selected from Cl, F, Br, I, OH, C₁₋₃ alkoxy, NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂, CH₂CH₂NH₂, CH₂CH₂NH(C₁₋₃ alkyl), and CH₂CH₂N(C₁₋₃ alkyl)₂; M is selected from the group:

J^(a) is NH or NR^(1a); Z is selected from (CR⁸R⁹)₁₋₄, (CR⁸R⁹)_(r)O(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)O(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)OC(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³C(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)OC(O)O(CR⁸R⁹)_(r), (CH₂)_(r)OC(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³C(O)O(CR⁸R⁹)_(r), (CH₂)_(r)NR³C(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)S(O)_(p)(CR⁸R⁹)_(r), (CCR⁸R⁹)_(r)SO₂NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³SO₂(CR⁸R⁹)_(r), and (CR⁸R⁹)_(r)NR³SO₂NR³(CR⁸R⁹)_(r), provided that Z does not form a N—N, N—O, N—S, NCH₂N, NCH₂O, or NCH₂S bond with the groups to which Z is attached; R^(1a) is selected from H, —(CH₂)_(r)—R¹′, —CH═CH—R¹′, NHCH₂R¹″, OCH₂R¹″, SCH₂R¹″, NH(CH₂)₂(CH₂)_(t)R¹′, O(CH₂)₂(CH₂)_(t)R¹′, and S(CH₂)₂(CH₂)_(t)R¹′; R¹′ is selected from H, C₁₋₃ alkyl, F, Cl, Br, I, —CN, —CHO, (CF2)_(r)CF₃, (CH₂)_(r)OR², NR²R^(2a), C(O)R^(2c), OC(O)R², (CF₂)_(r)CO₂R^(2c), S(O)_(p)R^(2b), NR²(CH₂)_(r)OR², C(═NR^(2c))NR²R^(2a), NR²C(O)R^(2b), NR²C(O)NHR^(2b), NR²C(O)₂R^(2a), OC(O)NR^(2a)R^(2b), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR², SO₂NR²R^(2a), NR²SO₂R^(2b), C₃₋₆ carbocycle substituted with 0-2 R⁴, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R⁴; R¹″ is selected from H, CH(CH₂OR²)₂, C(O)R^(2c), C(O)NR²R^(2a), S(O)R^(2b), S(O)₂R^(2b), and SO₂NR²R^(2a); R², at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b); R^(2a), at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl, benzyl, C₃₋₆ cycloalkylmethyl substituted with 0-2 R^(4b), C₃₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b); R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxy, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b); R^(2c), at each occurrence, is selected from CF₃, OH, C₁₋₄ alkoxy, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b); alternatively, R² and R^(2a), together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R^(4b)and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R³, at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl; R^(3a), at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl; R^(3b), at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl; R^(3c), at each occurrence, is selected from C₁₋₄ alkyl, and phenyl; A is selected from: C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R⁴; B is selected from: H, Y, X—Y, NR²R^(2a), and C(═NR²)NR²R^(2a), NR²C(═NR²)NR²R^(2a); X is selected from C₁₋₄ alkylene, —CR²(CR²R^(2b))(CH₂)_(t)—, —C(O)—, —C(═NR¹″)—, —CR²(NR¹″R²)—, —CR²(OR²)—, —CR²(SR²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —S(O)_(p)—, —S(O)_(p)CR²R^(2a)—, —CR²R^(2a)S(O)_(p)—, —S(O)₂NR²—, —NR²S (O)₂—, —NR²S (O)₂CR²R^(2a)—, —CR²R^(2a)S(O)₂NR²—, —NR²S(O)₂NR²—, —C(O)NR²—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—, —CR²R^(2a)NR²C(O)—, —NR²C(O)O—, —OC(O)NR²—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—; Y is selected from: (CH₂)_(r)NR²R^(2a), provided that X—Y do not form a N—N, O—N, or S—N bond, C₃₋₁₀ carbocycle substituted with 0-2 R^(4a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a); R⁴, at each occurrence, is selected from H, ═O, (CH₂)_(r)OR², F, Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), NR²C(O)NR²R^(2a), C(═NR²)NR²R^(2a), C(═NS(O)₂R⁵)NR²R^(2a), NHC(═NR²)NR²R^(2a), C(O)NHC(═NR²)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂—C₁₋₄ alkyl, NR²SO₂R⁵, S(O)_(p)R⁵, (CF₂)_(r)CF₃, NHCH₂R¹″, OCH₂R¹″, SCH₂R¹″, N(CH₂)₂(CH₂)_(t)R¹′, O(CH₂)₂(CH₂)_(t)R¹′, and S(CH₂)₂(CH₂)_(t)R¹′, alternatively, one R⁴ is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S; R^(4a), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR², (CH₂)_(r)—F, (CH₂)_(r)—Br, (CH₂)_(r)—Cl, Cl, Br, F, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), C(O)NH(CH₂)₂NR²R^(2a), NR²C(O)NR²R^(2a), C(═NR²)NR²R^(2a), NHC(═NR²)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂—C₁₋₄ alkyl, C(O)NHSO₂—C₁₋₄ alkyl, NR²SO₂R⁵, S(O)_(p)R⁵, and (CF₂)_(r)CF₃; alternatively, one R^(4a) is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-1 R⁵; R^(4b), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR³, F, Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³, (CH₂)_(r)C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), NR³C(O)NR³R^(3a), C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂-phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, and (CF₂)_(r)CF₃; R⁵, at each occurrence, is selected from CF₃, C₁₋₆ alkyl, phenyl substituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶; R⁶, at each occurrence, is selected from H, OH, (CH₂)_(r)OR², halo, C₁₋₄ alkyl, CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2b), NR²C(O)R^(2b), NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a), NR²SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl; R⁷, at each occurrence, is selected from H, OH, C₁₋₆ alkyl, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxy, C₁₋₄ alkoxycarbonyl, (CH₂)_(n)-phenyl, C₆₋₁₀ aryloxy, C₆₋₁₀ aryloxycarbonyl, C₆₋₁₀ arylmethylcarbonyl, C₁₋₄ alkylcarbonyloxy C₁₋₄ alkoxycarbonyl, C₆₋₁₀ arylcarbonyloxy C₁₋₄ alkoxycarbonyl, C₁₋₆ alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C₁₋₄ alkoxycarbonyl; R⁸, at each occurrence, is selected from H, C₁₋₆ alkyl and (CH₂)_(n)-phenyl; alternatively, R⁷ and R⁸ combine to form a 5 or 6 membered saturated, ring which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R9, at each occurrence, is selected from H, C₁₋₆ alkyl and (CH₂)_(n)-phenyl; n, at each occurrence, is selected from 0, 1, 2, and 3; m, at each occurrence, is selected from 0, 1, and 2; p, at each occurrence, is selected from 0, 1, and 2; r, at each occurrence, is selected from 0, 1, 2, and 3; s, at each occurrence, is selected from 0, 1, and 2; and, t, at each occurrence, is selected from 0, 1, 2, and
 3. 2. A compound according to claim 1, wherein: Z is selected from CH₂O, OCH₂, CH₂NH, NHCH₂, C(O), CH₂C(O), C(O)CH₂, NHC(O), C(O)NH, CH₂S(O)₂, S(O)₂(CH₂), SO₂NH, and NHSO₂, provided that Z does not form a N—N, N—O, NCH₂N, or NCH₂O bond with ring M or group A; A is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R⁴; phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl; B is selected from: H, Y, and X—Y; X is selected from C₁₋₄ alkylene, —C(O)—, —C(═NR)—, —CR²(NR²R^(2a))—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —C(O)NR²—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—, —CR²R^(2a)NR²C(O)—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—; Y is NR²R^(2a) or CH₂NR²R^(2a), provided that X—Y do not form a N—N or O—N bond; alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R^(4a); cylcopropyl, cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl; alternatively, Y is selected from the following bicyclic heteroaryl ring systems:

K is selected from O, S, NH, and N.
 3. A compound according to claim 2, wherein: Z is C(O)CH₂ and CONH, provided that Z does not form a N—N bond with group A; A is selected from phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2 R⁴; and, B is selected from Y, X—Y, phenyl, pyrrolidino, morpholino, 1,2,3-triazolyl, and imidazolyl, and is substituted with 0-1 R^(4a); X is selected from CH₂, —C(O)—, and O; Y is NR²R^(2a) or CH₂NR²R^(2a), provided that X—Y does not form an O—N bond; alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R^(4a); phenyl, piperazinyl, pyridyl, pyrimidyl, morpholinyl, pyrrolidinyl, imidazolyl, and 1,2,3-triazolyl; R², at each occurrence, is selected from H, CF₃, CH₃, benzyl, and phenyl; R^(2a), at each occurrence, is selected from H, CF₃, CH₃, CH(CH₃)₂, cyclopropylmethyl, benzyl, and phenyl; alternatively, R² and R^(2a) combine to form a ring system substituted with 0-2 R^(4b), the ring system being selected from pyrrolidinyl, piperazinyl and morpholino; R⁴, at each occurrence, is selected from OH, (CH₂)_(r)OR², Cl, F, C₁₋₄ alkyl, (CH₂)_(r)NR²R^(2a), and (CF₂)_(r)CF₃; R^(4a) is selected from Cl, F, C₁₋₄ alkyl, CF₃, (CH₂)_(r)NR²R^(2a), S(O)_(p)R⁵, SO₂NR²R^(2a), and 1-CF₃-tetrazol-2-yl; R^(4b), at each occurrence, is selected from OH, Cl, F, CH₃, and CF₃; R⁵, at each occurrence, is selected from CF₃, C₁₋₆ alkyl, phenyl, and benzyl; R⁷, at each occurrence, is selected from H, CH₃, and CH₂CH₃; and, R⁸, at each occurrence, is selected from H and CH₃.
 4. A compound according to claim 3, wherein: R^(1a) is absent or is —(CH₂)_(r)—R¹′; R¹′ is selected from H, C₁₋₃ alkyl, F, Cl, —CN, CF₃, (CH₂)_(r)OR², NR²R^(2a), C(O)R^(2c), OC(O)R², S(O)_(p)R^(2b), NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a), C₃₋₆ carbocycle substituted with 0-2 R^(4a), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a); A is selected from the group: phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl; and, B is selected from the group: 2-CF₃-phenyl, 2-(aminosulfonyl)phenyl, 2-(methylaminosulfonyl)phenyl, 2-(dimethylaminosulfonyl)phenyl, 1-pyrrolidinocarbonyl, 2-(methylsulfonyl)phenyl, 2-(N,N-dimethylaminomethyl)phenyl, 2-(isopropylaminomethyl)phenyl, 2-(cyclopropylaminomethyl)phenyl, 2-(N-pyrrolidinylmethyl)phenyl, 2-(3-hydroxy-N-pyrrolidinylmethyl)phenyl, 4-morpholino, 2-(1′-CF₃-tetrazol-2-yl)phenyl, 4-morpholinocarbonyl, 1-methyl-2-imidazolyl, 2-methyl-1-imidazolyl, 5-methyl-1-imidazolyl, 2-(N,N-dimethylaminomethyl)imidazolyl, 2-methylsulfonyl-1-imidazolyl and, 5-methyl-1,2,3-triazolyl.
 5. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
 6. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 2 or a pharmaceutically acceptable salt thereof.
 7. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 3 or a pharmaceutically acceptable salt thereof.
 8. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 4 or a pharmaceutically acceptable salt thereof.
 9. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
 10. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 2 or a pharmaceutically acceptable salt thereof.
 11. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 3 or a pharmaceutically acceptable salt thereof.
 12. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 4 or a pharmaceutically acceptable salt thereof.
 13. A method according to claim 9, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, aterial cerebrovascular thromboembolic disorders, venous cerebrovascular thromboembolic disorders, unstable angina, first myocardial infarction, recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary arterial thrombosis, cerebral arterial thrombosis, cerebral embolism, kidney embolism, and pulmonary embolism.
 14. A method according to claim 10, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, aterial cerebrovascular thromboembolic disorders, venous cerebrovascular thromboembolic disorders, unstable angina, first myocardial infarction, recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary arterial thrombosis, cerebral arterial thrombosis, cerebral embolism, kidney embolism, and pulmonary embolism.
 15. A method according to claim 11, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, aterial cerebrovascular thromboembolic disorders, venous cerebrovascular thromboembolic disorders, unstable angina, first myocardial infarction, recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary arterial thrombosis, cerebral arterial thrombosis, cerebral embolism, kidney embolism, and pulmonary embolism.
 16. A method according to claim 12, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, aterial cerebrovascular thromboembolic disorders, venous cerebrovascular thromboembolic disorders, unstable angina, first myocardial infarction, recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary arterial thrombosis, cerebral arterial thrombosis, cerebral embolism, kidney embolism, and pulmonary embolism. 